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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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17 pages, 256 KiB  
Opinion
On the Trail of the Longest Plant RNA Virus: Citrus Tristeza Virus
by Moshe Bar-Joseph
Viruses 2025, 17(4), 508; https://doi.org/10.3390/v17040508 - 31 Mar 2025
Viewed by 448
Abstract
The devastating tristeza epidemic swept through South American citrus groves in the 1930s and subsequently spread to most citrus-growing regions worldwide, causing varying degrees of damage and prompting significant changes in citrus cultivation practices. The causal agent of the disease, citrus tristeza virus [...] Read more.
The devastating tristeza epidemic swept through South American citrus groves in the 1930s and subsequently spread to most citrus-growing regions worldwide, causing varying degrees of damage and prompting significant changes in citrus cultivation practices. The causal agent of the disease, citrus tristeza virus (CTV), belongs to the genus Closterovirus in the family Closteroviridae. CTV virions are approximately two microns long and possess the largest known positive-strand RNA genome in plants, spanning 19.3 kb. The history of tristeza disease and CTV’s molecular biology and taxonomic relationships have been extensively reviewed in the scientific literature. This paper primarily focuses on the author’s personal experiences with tristeza disease and its causal agent over the past six decades. The journey began during a period when biological indexing was the primary diagnostic tool. It later progressed through the isolation of purified CTV particles, which served as a practical diagnostic tool for CTV suppression efforts in Israel during the 1970s. However, biological indexing was first replaced by electron microscopy, followed by ELISA procedures; both were eventually abandoned after it was discovered that many ELISA-positive infections were caused by symptomless CTV isolates, even on trees grafted onto sour orange rootstocks. In retrospect, my work on CTV can be categorized into three main phases. It began with the biological phase, inherited from earlier generations of citrus virologists, followed by the isolation and partial characterization of CTV virions, and culminated in the genomic era. While we live in an age of remarkable biotechnological achievements, my recommendation for future CTV research is to integrate both biological and genomic approaches rather than viewing them as mutually exclusive. This is particularly important for economically significant pathogens such as CTV, which should be studied continuously as both biological agents and molecular pathogens. Full article
(This article belongs to the Special Issue Citrus Viral Diseases: Advances in Knowledge and Technologies and Their Containment Measures)
13 pages, 2250 KiB  
Article
La Jolla Virus: The Pathology and Transmission in Its Host Drosophila suzukii
by Ibrahim Abdelhafiz, Tobias Kessel, Andreas Vilcinskas and Kwang-Zin Lee
Viruses 2025, 17(3), 408; https://doi.org/10.3390/v17030408 - 13 Mar 2025
Viewed by 522
Abstract
Drosophila suzukii, commonly known as spotted-wing drosophila, has emerged as a highly destructive pest in global fruit and wine production. The effectiveness of chemical control is significantly compromised by rapid resistance development and a limited range of insecticide options. Biological control presents [...] Read more.
Drosophila suzukii, commonly known as spotted-wing drosophila, has emerged as a highly destructive pest in global fruit and wine production. The effectiveness of chemical control is significantly compromised by rapid resistance development and a limited range of insecticide options. Biological control presents a promising sustainable alternative. Our previous work suggested the La Jolla Virus (LJV) as a suitable candidate for the development of an insect virus-based control option. Here, we characterized the natural transmission and pathology of the virus. We tested various modes of horizontal transmission, including airborne, venereal and oral, and fecal routes. To understand LJV pathology in infected flies, we studied feeding behavior and demonstrated changes in food absorption compared to non-infected flies. We also investigated the impact on fecundity and egg-to-adult success rate. Altogether, these results collectively improve our understanding of LJV transmission in natural populations and the implication of infected flies in food ingestion and overall fitness. Full article
(This article belongs to the Special Issue Insect Viruses and Pest Management, the Third Edition)
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20 pages, 5726 KiB  
Article
Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors
by Hasset Tibebe, Dacia Marquez, Aidan McGraw, Sophia Gagliardi, Cailyn Sullivan, Grace Hillmer, Kedhar Narayan, Coco Izumi, Adleigh Keating and Taisuke Izumi
Viruses 2025, 17(3), 400; https://doi.org/10.3390/v17030400 - 12 Mar 2025
Viewed by 2134
Abstract
The “Kick and Kill” strategy, which aims to reactivate latent HIV reservoirs and facilitate the clearance of reactivated HIV-infected cells, has yet to achieve a functional cure due to the limited efficacy of current latency reversal agents. This study evaluates the combination efficacy [...] Read more.
The “Kick and Kill” strategy, which aims to reactivate latent HIV reservoirs and facilitate the clearance of reactivated HIV-infected cells, has yet to achieve a functional cure due to the limited efficacy of current latency reversal agents. This study evaluates the combination efficacy of histone deacetylase (HDAC) inhibitor with poly(ADP-ribose) polymerase (PARP) inhibitor in latency reversal and immune-mediated clearance. Latently infected J-Lat cells and dual-fluorescent HIV-infected primary CD4 T cells were treated with the HDAC inhibitor (vorinostat) and one of four PARP inhibitors (olaparib, rucaparib, niraparib, or talazoparib). PARP inhibitors, when administered alone, showed no latency reversal activity. However, when combined with vorinostat, their efficacy increased threefold compared to vorinostat alone. This effect was mediated by the inhibition of tankyrase, a PARP superfamily member, which modulates the Hippo signaling pathway. In HIVGR670-infected primary cells, the combination reduced the reservoir size by 67%. In addition, talazoparib alone significantly reduced actively infected cells by 50%. Talazoparib-treated peripheral blood mononuclear cells co-cultured with K562 cells demonstrated enhanced NK-cell-mediated cytotoxicity, with a 10% reduction in K562 cell viability. These findings demonstrate that combining HDAC and PARP inhibitors augments latency reversal and reservoir reduction. With both the HDAC inhibitors and PARP inhibitors used in this study approved by the FDA for cancer treatment, this combination therapy holds strong potential for rapid clinical integration, contingent upon the confirmation of efficacy and safety in ongoing in vivo studies. Full article
(This article belongs to the Special Issue Novel Strategies to Identify and Eliminate Latent HIV Cells)
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16 pages, 5313 KiB  
Article
The In Situ Structure of T-Series T1 Reveals a Conserved Lambda-Like Tail Tip
by Yuan Chen, Hao Xiao, Junquan Zhou, Zeng Peng, Yuning Peng, Jingdong Song, Jing Zheng and Hongrong Liu
Viruses 2025, 17(3), 351; https://doi.org/10.3390/v17030351 - 28 Feb 2025
Viewed by 566
Abstract
It is estimated that over 60% of known tailed phages are siphophages, which are characterized by a long, flexible, and non-contractile tail. Nevertheless, entire high-resolution structures of siphophages remain scarce. Using cryo-EM, we resolved the structures of T-series siphophage T1, encompassing its head, [...] Read more.
It is estimated that over 60% of known tailed phages are siphophages, which are characterized by a long, flexible, and non-contractile tail. Nevertheless, entire high-resolution structures of siphophages remain scarce. Using cryo-EM, we resolved the structures of T-series siphophage T1, encompassing its head, connector complex, tail tube, and tail tip, at near-atomic resolution. The density maps enabled us to build the atomic models for the majority of T1 proteins. The T1 head comprises 415 copies of the major capsid protein gp47, arranged into an icosahedron with a triangulation number of seven, decorated with 80 homologous trimers and 60 heterotrimers along the threefold and quasi-threefold axes of the icosahedron. The T1 connector complex is composed of two dodecamers (a portal and an adaptor) and two hexamers (a stopper and a tail terminator). The flexible tail tube comprises approximately 34 hexameric rings of tail tube. The extensive disulfide bond network along the successive tail rings may mediate the flexible bending. The distal tip of T1, which is cone-shaped and assembled by proteins gp33, gp34, gp36, gp37, and gp38, displays structural similarity to that of phage lambda. In conjunction with previous studies of lambda-like siphophages, our structure will facilitate further exploration of the structural and mechanistic aspects of lambda-like siphophages. Full article
(This article belongs to the Section Bacterial Viruses)
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16 pages, 2806 KiB  
Article
Molecular Dissection of Symptom Determinants in Tomato Leaf Curl New Delhi Virus in Zucchini Through Mechanical Transmission
by Thuy T. B. Vo, Eui-Joon Kil, Marjia Tabassum, Bupi Nattanong, Muhammad Amir Qureshi, Hyo-Jin Im, Giuseppe Parrella, Taek-Kyun Lee and Sukchan Lee
Viruses 2025, 17(3), 294; https://doi.org/10.3390/v17030294 - 20 Feb 2025
Viewed by 539
Abstract
Among begomovirus species, tomato leaf curl New Delhi virus (ToLCNDV) is significant and stands out as a mechanically transmissible bipartite begomovirus originating from the Old World. However, the mechanisms underlying the mechanical transmission of different ToLCNDV strains remain understudied, as their natural transmission [...] Read more.
Among begomovirus species, tomato leaf curl New Delhi virus (ToLCNDV) is significant and stands out as a mechanically transmissible bipartite begomovirus originating from the Old World. However, the mechanisms underlying the mechanical transmission of different ToLCNDV strains remain understudied, as their natural transmission occurs via insect vectors. In this study, we investigated the mechanical transmissibility of two ToLCNDVs, one from Italy and another from Pakistan, in host plants. Several cucurbit species were screened, and symptom differences between the two ToLCNDV clones were observed only in zucchini when subjected to rubbing inoculation. The Italian isolate (ToLCNDV-ES) induced typical disease symptoms such as leaf curling, yellow mosaic, and internode stunting, whereas a normal phenotype was observed in zucchini mechanically infected with ToLCNDV-In (Pakistani isolate). Subsequently, a gene-swapping experiment between the two ToLCNDVs was conducted, and ToLCNDV-ES DNA-B was identified as a crucial factor in mechanical transmission. We then constructed chimeric mutant clones based on the DNA-B sequence and assessed their ability to induce symptoms in zucchini. These results indicated that the nuclear shuttle protein is a determinant of symptom development during ToLCNDV mechanical transmission. Moreover, several defense-related host genes showed significant changes in relative expression in different ToLCNDV clones, indicating their potential role in disease symptom development through the mechanical transmission of ToLCNDV. This is the first report comparing the mechanical transmissibility of two isolates of different ToLCNDV strains from the Mediterranean region and the Indian subcontinent in the same host plant, providing new insights into the virus’s pathogenicity across different geographic regions. Full article
(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)
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18 pages, 2584 KiB  
Article
Disease Tolerance in ‘Anaheim’ Pepper to PepGMV-D Strain Involves Complex Interactions Between the Movement Protein Putative Promoter Region and Unknown Host Factors
by Cecilia Hernández-Zepeda and Judith K. Brown
Viruses 2025, 17(2), 268; https://doi.org/10.3390/v17020268 - 15 Feb 2025
Viewed by 503
Abstract
Pepper golden mosaic virus (PepGMV) is a bipartite begomovirus of pepper and tomato from North America. In ‘Anaheim’ pepper plants PepGMV-Mo strain (Mo) causes systemic yellow foliar mosaic symptoms, while PepGMV-D strain (D) causes distortion of 1st–6th expanding leaves, and asymptomatic infection of [...] Read more.
Pepper golden mosaic virus (PepGMV) is a bipartite begomovirus of pepper and tomato from North America. In ‘Anaheim’ pepper plants PepGMV-Mo strain (Mo) causes systemic yellow foliar mosaic symptoms, while PepGMV-D strain (D) causes distortion of 1st–6th expanding leaves, and asymptomatic infection of subsequently developing leaves, like other known ‘recovery’ phenotypes. Infections established with DNA-A Mo and D components expressing red-shifted green fluorescent protein in place of coat protein and in situ hybridization, showed PepGMV-Mo localized to phloem and mesophyll cells, while -D was mesophyll restricted. Alignment of PepGMV-Mo and -D DNA-B components revealed three indels upstream of the BC1 gene that encodes the movement protein (MP). To determine if this non-coding region (*BC1) D-strain MP putative promoter contributed to ‘recovery’, plants were inoculated with chimeric DNA-B Mo/D components harboring reciprocally exchanged *BC1, and wild-type DNA-A Mo and D components. Symptoms were reminiscent but not identical to wild-type -Mo or -D infection, respectively, suggesting ‘recovery’ cannot be attributed solely to the *BC1. Both BC1 and D*BC1 were targeted by post-transcriptional gene silencing; however, ‘recovered’ leaves accumulated fewer transcripts and 21–24 nt vsiRNAs. Thus, inefficient in planta movement of PepGMV-D is associated with a non-pepper-adapted ‘defective’ BC1 that facilitates hyper-efficient PTGS, leading to BC1 transcript degradation that in turn limits virus spread, thereby recapitulating disease ‘tolerance’. Full article
(This article belongs to the Special Issue Plant Virus Interactions with Hosts: Mechanisms and Applications)
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15 pages, 3034 KiB  
Article
Impacts of Antiretroviral Therapy on the Oral Microbiome and Periodontal Health of Feline Immunodeficiency Virus-Positive Cats
by Laura Bashor, Jennifer E. Rawlinson, Christopher P. Kozakiewicz, Elisa Behzadi, Craig Miller, Jeffrey Kim, Megan Cierzan, Mary Nehring, Scott Carver, Zaid Abdo and Sue VandeWoude
Viruses 2025, 17(2), 257; https://doi.org/10.3390/v17020257 - 13 Feb 2025
Viewed by 1406
Abstract
Feline immunodeficiency virus (FIV) is the domestic cat analogue of HIV infection in humans. Both viruses induce oral disease in untreated individuals, with clinical signs that include gingivitis and periodontal lesions. Oral disease manifestations in HIV patients are abated by highly effective combination [...] Read more.
Feline immunodeficiency virus (FIV) is the domestic cat analogue of HIV infection in humans. Both viruses induce oral disease in untreated individuals, with clinical signs that include gingivitis and periodontal lesions. Oral disease manifestations in HIV patients are abated by highly effective combination antiretroviral therapy (cART), though certain oral manifestations persist despite therapy. Microorganisms associated with oral cavity opportunistic infections in patients with HIV cause similar pathologies in cats. To further develop this model, we evaluated characteristics of feline oral health and the oral microbiome during experimental FIV infection over an 8-month period following cART. Using 16S rRNA sequencing, we evaluated gingival bacterial communities at four timepoints in uninfected and FIV-infected cats treated with either cART or placebo. Comprehensive oral examinations were also conducted by a veterinary dental specialist over the experimental period. Gingival inflammation was higher in FIV-infected cats treated with placebo compared to cART-treated cats and the controls at the study endpoint. Oral microbiome alpha diversity increased in all groups, while beta diversity differed among treatment groups, documenting a significant effect of cART therapy on microbiome community composition. This finding has not previously been reported, and indicates cART ameliorates immunodeficiency virus-associated oral disease via the preservation of oral mucosal microbiota. Further, this study illustrates the value of the FIV animal model for investigations of mechanistic associations and therapeutic interventions for HIV’s oral manifestations. Full article
(This article belongs to the Section Animal Viruses)
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35 pages, 2508 KiB  
Review
Tobacco Mosaic Virus Movement: From Capsid Disassembly to Transport Through Plasmodesmata
by Amr Ibrahim, Nobumitsu Sasaki, James E. Schoelz and Richard S. Nelson
Viruses 2025, 17(2), 214; https://doi.org/10.3390/v17020214 - 31 Jan 2025
Cited by 1 | Viewed by 1581
Abstract
Determining mechanisms to establish an initial infection and form intracellular complexes for accumulation and movement of RNA plant viruses are important areas of study in plant virology. The impact of these findings on the basic understanding of plant molecular virology and its application [...] Read more.
Determining mechanisms to establish an initial infection and form intracellular complexes for accumulation and movement of RNA plant viruses are important areas of study in plant virology. The impact of these findings on the basic understanding of plant molecular virology and its application in agriculture is significant. Studies with tobacco mosaic virus (TMV) and related tobamoviruses often provide important foundational knowledge for studies involving other viruses. Topics discussed here include capsid disassembly, establishment of a virus replication complex (VRC), and transport of the VRCs or virus components within the cell to locations at the plasmodesmata for intercellular virus RNA (vRNA) movement. Seminal findings with TMV and related tobamoviruses include detecting co-translational disassembly of the vRNA from the virus rod, full sequencing of genomic vRNA and production of infectious transcript for genetic studies determining virus components necessary for intercellular movement, and biochemical and cell biological studies determining the host factors, protein and membrane, needed for replication and movement. This review highlights many of the studies through the years on TMV and selected tobamoviruses that have impacted not only our understanding of tobamovirus accumulation and movement but also that of other plant viruses. Full article
(This article belongs to the Special Issue Tobamoviruses: Molecular Aspects and Resistance Regulation—a Special Issue Commemorating 125 Years of Research on Tobamoviruses)
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17 pages, 9817 KiB  
Article
Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance
by Haydar Witwit, Beatrice Cubitt, Roaa Khafaji, Esteban M. Castro, Miguel Goicoechea, Maria M. Lorenzo, Rafael Blasco, Luis Martinez-Sobrido and Juan C. de la Torre
Viruses 2025, 17(1), 92; https://doi.org/10.3390/v17010092 - 13 Jan 2025
Cited by 1 | Viewed by 2025
Abstract
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which [...] Read more.
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088. Both MMF and IMP-1088 drugs exhibited strong dose-dependent antiviral activity against VACV and mpox, and potent synergistic effects in conjunction with TPOXX. Our findings support combination therapy of direct-acting (TPOXX) and host-targeted (MMF and IMP-1088) antivirals as a promising approach to treat mpox and prevent the emergence and spread of TPOXX-resistant MPXV variants. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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39 pages, 7731 KiB  
Article
Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates
by Gregory S. Lambert, Rebecca J. Kaddis Maldonado and Leslie J. Parent
Viruses 2025, 17(1), 97; https://doi.org/10.3390/v17010097 - 13 Jan 2025
Viewed by 1116
Abstract
Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at [...] Read more.
Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization. We observed that the psi (Ψ) packaging signal and the dimerization initiation sequence (DIS) had stabilizing effects on RSV Gag condensates, while RNAs lacking these features promoted or antagonized condensation, depending on local protein concentration and condensate architecture. An RNA containing Ψ, DIS, and the dimerization linkage structure (DLS) that is capable of stable dimer formation was observed to act as a bridge between RSV Gag condensates. These observations suggest additional, condensate-related roles for Gag-Ψ binding, gRNA dimerization, and Gag dimerization/multimerization in gRNA selection and packaging, representing a significant step forward in our understanding of how these interactions collectively facilitate efficient genome packaging. Full article
(This article belongs to the Special Issue 12th International Retroviral Symposium: Assembly, Maturation and Uncoating)
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22 pages, 15117 KiB  
Article
The Transcriptional Program of Staphylococcus aureus Phage K Is Affected by a Host rpoC Mutation That Confers Phage K Resistance
by Rohit Kongari, Melissa D. Ray, Susan M. Lehman, Roger D. Plaut, Deborah M. Hinton and Scott Stibitz
Viruses 2024, 16(11), 1773; https://doi.org/10.3390/v16111773 - 13 Nov 2024
Viewed by 1785
Abstract
To better understand host–phage interactions and the genetic bases of phage resistance in a model system relevant to potential phage therapy, we isolated several spontaneous mutants of the USA300 S. aureus clinical isolate NRS384 that were resistant to phage K. Six of these [...] Read more.
To better understand host–phage interactions and the genetic bases of phage resistance in a model system relevant to potential phage therapy, we isolated several spontaneous mutants of the USA300 S. aureus clinical isolate NRS384 that were resistant to phage K. Six of these had a single missense mutation in the host rpoC gene, which encodes the RNA polymerase β’ subunit. To examine the hypothesis that mutations in the host RNA polymerase affect the transcription of phage genes, we performed RNA-seq analysis on total RNA samples collected from NRS384 wild-type (WT) and rpoCG17D mutant cultures infected with phage K, at different timepoints after infection. Infection of the WT host led to a steady increase of phage transcription relative to the host. Our analysis allowed us to define 53 transcriptional units and to categorize genes based on their temporal expression patterns. Predicted promoter sequences defined by conserved −35, −10, and, in some cases, extended −10 elements, were found upstream of early and middle genes. However, in many cases, sequences upstream of late genes did not contain clear, complete, canonical promoter sequences, suggesting that factors in addition to host RNA polymerase are required for their expression. Infection of the rpoCG17D mutant host led to a transcriptional pattern that was similar to that of the WT at early timepoints. However, beginning at 20 min after infection, transcription of late genes (such as phage structural genes and host lysis genes) was severely reduced. Our data indicate that the rpoCG17D mutation prevents the expression of phage late genes, resulting in a failed infection cycle for phage K. In addition to illuminating the global transcriptional landscape of phage K throughout the infection cycle, this study will inform our investigations into the basis of phage K’s control of its transcriptional program as well as mechanisms of phage resistance. Full article
(This article belongs to the Section Bacterial Viruses)
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21 pages, 6333 KiB  
Article
Multiplex Microscopy Assay for Assessment of Therapeutic and Serum Antibodies against Emerging Pathogens
by Nuno Sartingen, Vanessa Stürmer, Matthias Kaltenböck, Thorsten G. Müller, Paul Schnitzler, Anna Kreshuk, Hans-Georg Kräusslich, Uta Merle, Frauke Mücksch, Barbara Müller, Constantin Pape and Vibor Laketa
Viruses 2024, 16(9), 1473; https://doi.org/10.3390/v16091473 - 17 Sep 2024
Viewed by 2969
Abstract
The emergence of novel pathogens, exemplified recently by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for rapidly deployable and adaptable diagnostic assays to assess their impact on human health and guide public health responses in future pandemics. In this [...] Read more.
The emergence of novel pathogens, exemplified recently by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for rapidly deployable and adaptable diagnostic assays to assess their impact on human health and guide public health responses in future pandemics. In this study, we developed an automated multiplex microscopy assay coupled with machine learning-based analysis for antibody detection. To achieve multiplexing and simultaneous detection of multiple viral antigens, we devised a barcoding strategy utilizing a panel of HeLa-based cell lines. Each cell line expressed a distinct viral antigen, along with a fluorescent protein exhibiting a unique subcellular localization pattern for cell classification. Our robust, cell segmentation and classification algorithm, combined with automated image acquisition, ensured compatibility with a high-throughput approach. As a proof of concept, we successfully applied this approach for quantitation of immunoreactivity against different variants of SARS-CoV-2 spike and nucleocapsid proteins in sera of patients or vaccinees, as well as for the study of selective reactivity of monoclonal antibodies. Importantly, our system can be rapidly adapted to accommodate other SARS-CoV-2 variants as well as any antigen of a newly emerging pathogen, thereby representing an important resource in the context of pandemic preparedness. Full article
(This article belongs to the Special Issue Microscopy Methods for Virus Research)
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31 pages, 115227 KiB  
Article
Translation of Overlapping Open Reading Frames Promoted by Type 2 IRESs in Avian Calicivirus Genomes
by Yani Arhab, Tatyana V. Pestova and Christopher U. T. Hellen
Viruses 2024, 16(9), 1413; https://doi.org/10.3390/v16091413 - 4 Sep 2024
Cited by 2 | Viewed by 2114
Abstract
Caliciviruses have positive-sense RNA genomes, typically with short 5′-untranslated regions (5′UTRs) that precede the long open reading frame 1 (ORF1). Exceptionally, some avian caliciviruses have long 5′UTRs containing a picornavirus-like internal ribosomal entry site (IRES), which was likely acquired by horizontal gene transfer. [...] Read more.
Caliciviruses have positive-sense RNA genomes, typically with short 5′-untranslated regions (5′UTRs) that precede the long open reading frame 1 (ORF1). Exceptionally, some avian caliciviruses have long 5′UTRs containing a picornavirus-like internal ribosomal entry site (IRES), which was likely acquired by horizontal gene transfer. Here, we identified numerous additional avian calicivirus genomes with IRESs, predominantly type 2, and determined that many of these genomes contain a ~200–300 codon-long ORF (designated ORF1*) that overlaps the 5′-terminal region of ORF1. The activity of representative type 2 IRESs from grey teal calicivirus (GTCV) and Caliciviridae sp. isolate yc-13 (RaCV1) was confirmed by in vitro translation. Toeprinting showed that in cell-free extracts and in vitro reconstituted reactions, ribosomal initiation complexes assembled on the ORF1* initiation codon and at one or two AUG codons in ORF1 at the 3′-border and/or downstream of the IRES. Initiation at all three sites required eIF4A and eIF4G, which bound to a conserved region of the IRES; initiation on the ORF1* and principal ORF1 initiation codons involved eIF1/eIF1A-dependent scanning from the IRES’s 3′-border. Initiation on these IRESs was enhanced by the IRES trans-acting factors (ITAFs) Ebp1/ITAF45, which bound to the apical subdomain Id of the IRES, and PTB (GTCV) or PCBP2 (RaCV1). Full article
(This article belongs to the Special Issue Viral Strategies and Cellular Countermeasures that Regulate mRNA Access to the Translation Apparatus)
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10 pages, 3633 KiB  
Communication
Resistance of the CRISPR-Cas13a Gene-Editing System to Potato Spindle Tuber Viroid Infection in Tomato and Nicotiana benthamiana
by Ying Wei Khoo, Qingsong Wang, Shangwu Liu, Binhui Zhan, Tengfei Xu, Wenxia Lv, Guangjing Liu, Shifang Li and Zhixiang Zhang
Viruses 2024, 16(9), 1401; https://doi.org/10.3390/v16091401 - 31 Aug 2024
Viewed by 1797
Abstract
Gene-editing technology, specifically the CRISPR-Cas13a system, has shown promise in breeding plants resistant to RNA viruses. This system targets RNA and, theoretically, can also combat RNA-based viroids. To test this, the CRISPR-Cas13a system was introduced into tomato plants via transient expression and into [...] Read more.
Gene-editing technology, specifically the CRISPR-Cas13a system, has shown promise in breeding plants resistant to RNA viruses. This system targets RNA and, theoretically, can also combat RNA-based viroids. To test this, the CRISPR-Cas13a system was introduced into tomato plants via transient expression and into Nicotiana benthamiana through transgenic methods, using CRISPR RNAs (crRNAs) targeting the conserved regions of both sense and antisense genomes of potato spindle tuber viroid (PSTVd). In tomato plants, the expression of CRISPR-Cas13a and crRNAs substantially reduced PSTVd accumulation and alleviated disease symptoms. In transgenic N. benthamiana plants, the PSTVd levels were lower as compared to wild-type plants. Several effective crRNAs targeting the PSTVd genomic RNA were also identified. These results demonstrate that the CRISPR-Cas13a system can effectively target and combat viroid RNAs, despite their compact structures. Full article
(This article belongs to the Special Issue Crop Resistance to Viral Infections)
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16 pages, 3588 KiB  
Article
Parainfluenza Virus 5 V Protein Blocks Interferon Gamma-Mediated Upregulation of NK Cell Inhibitory Ligands and Improves NK Cell Killing of Neuroblastoma Cells
by Elisabeth M. Shiffer, Jeremiah L. Oyer, Alicja J. Copik and Griffith D. Parks
Viruses 2024, 16(8), 1270; https://doi.org/10.3390/v16081270 - 9 Aug 2024
Viewed by 1690
Abstract
Natural killer (NK) cells can be effective immunotherapeutic anti-cancer agents due to their ability to selectively target and kill tumor cells. This activity is modulated by the interaction of NK cell receptors with inhibitory ligands on the surface of target cells. NK cell [...] Read more.
Natural killer (NK) cells can be effective immunotherapeutic anti-cancer agents due to their ability to selectively target and kill tumor cells. This activity is modulated by the interaction of NK cell receptors with inhibitory ligands on the surface of target cells. NK cell inhibitory ligands can be upregulated on tumor cell surfaces in response to interferon-gamma (IFN-γ), a cytokine which is produced by activated NK cells. We hypothesized that the resistance of tumor cells to NK cell killing could be overcome by expression of the parainfluenza virus 5 (PIV5) V protein, which has known roles in blocking IFN-γ signaling. This was tested with human PM21-NK cells produced through a previously developed particle-based method which yields superior NK cells for immunotherapeutic applications. Infection of human SK-N-SH neuroblastoma cells with PIV5 blocked IFN-γ-mediated upregulation of three NK cell inhibitory ligands and enhanced in vitro killing of these tumor cells by PM21-NK cells. SK-N-SH cells transduced to constitutively express the V protein alone were resistant to IFN-γ-mediated increases in cell surface expression of NK cell inhibitory ligands. Real-time in vitro cell viability assays demonstrated that V protein expression in SK-N-SH cells was sufficient to increase PM21-NK cell-mediated killing. Toward a potential therapeutic application, transient lentiviral delivery of the V gene also enhanced PM21-NK cell killing in vitro. Our results provide the foundation for novel therapeutic applications of V protein expression in combination with ex vivo NK cell therapy to effectively increase the killing of tumor cells. Full article
(This article belongs to the Special Issue Viruses 2024—A World of Viruses)
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13 pages, 1551 KiB  
Article
Challenges in the Diagnosis of SARS-CoV-2 Infection in the Nervous System
by Samya Jezine Da Silva, Mauro Jorge Cabral-Castro, Cássia Cristina Alves Gonçalves, Diana Mariani, Orlando Ferreira, Amílcar Tanuri and Marzia Puccioni-Sohler
Viruses 2024, 16(8), 1247; https://doi.org/10.3390/v16081247 - 3 Aug 2024
Cited by 1 | Viewed by 1315
Abstract
Neurological involvement has been widely reported in SARS-CoV-2 infection. However, viral identification in the cerebrospinal fluid (CSF) is rarely found. The aim of this study is to evaluate the accuracy of virological and immunological biomarkers in CSF for the diagnosis of neuroCOVID-19. We [...] Read more.
Neurological involvement has been widely reported in SARS-CoV-2 infection. However, viral identification in the cerebrospinal fluid (CSF) is rarely found. The aim of this study is to evaluate the accuracy of virological and immunological biomarkers in CSF for the diagnosis of neuroCOVID-19. We analyzed 69 CSF samples from patients with neurological manifestations: 14 with suspected/confirmed COVID-19, with 5 additional serial CSF samples (group A), and as a control, 50 non-COVID-19 cases (group B—26 with other neuroinflammatory diseases; group C—24 with non-inflammatory diseases). Real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) was used to determine SARS-CoV-2, and specific IgG, IgM, neopterin, and protein 10 induced by gamma interferon (CXCL-10) were evaluated in the CSF samples. No samples were amplified for SARS-CoV-2 by real-time RT-PCR. The sensitivity levels of anti-SARS-CoV-2 IgG and IgM were 50% and 14.28%, respectively, with 100% specificity for both tests. CXCL-10 showed high sensitivity (95.83%) and specificity (95.83%) for detection of neuroinflammation. Serial CSF analysis showed an association between the neuroinflammatory biomarkers and outcome (death and hospital discharge) in two cases (meningoencephalitis and rhombencephalitis). The detection of SARS-CoV-2 RNA and specific immunoglobulins in the CSF can be used for neuroCOVID-19 confirmation. Additionally, CXCL-10 in the CSF may contribute to the diagnosis and monitoring of neuroCOVID-19. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Viral Infection)
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23 pages, 3415 KiB  
Article
Temporal Dynamics of Purinergic Receptor Expression in the Lungs of Marek’s Disease (MD) Virus-Infected Chickens Resistant or Susceptible to MD
by Haji Akbar and Keith W. Jarosinski
Viruses 2024, 16(7), 1130; https://doi.org/10.3390/v16071130 - 14 Jul 2024
Viewed by 1191
Abstract
Marek’s disease virus (MDV) is an economic concern for the poultry industry due to its poorly understood pathophysiology. Purinergic receptors (PRs) are potential therapeutic targets for viral infections, including herpesviruses, prompting our investigation into their role in MDV pathogenesis. The current study is [...] Read more.
Marek’s disease virus (MDV) is an economic concern for the poultry industry due to its poorly understood pathophysiology. Purinergic receptors (PRs) are potential therapeutic targets for viral infections, including herpesviruses, prompting our investigation into their role in MDV pathogenesis. The current study is part of an experimental series analyzing the expression of PRs during MDV infection. To address the early or short-acting P2 PR responses during natural MDV infection, we performed an “exposure” experiment where age-matched chickens were exposed to experimentally infected shedders to initiate natural infection. In addition, select non-PR regulatory gene responses were measured. Two groups of naïve contact chickens (n = 5/breed/time point) from MD-resistant (White Leghorns: WL) and -susceptible (Pure Columbian) chicken lines were housed separately with experimentally infected PC (×PC) and WL (×WL) chickens for 6 or 24 h. Whole lung lavage cells (WLLC) were collected, RNA was extracted, and RT-qPCR assays were used to measure specific PR responses. In addition, other potentially important markers in pathophysiology were measured. Our study revealed that WL chickens exhibited higher P1 PR expression during natural infection. WL chickens also showed higher expression of P1A3 and P2X3 at 6 and 24 h when exposed to PC-infected chickens. P2X5 and P2Y1 showed higher expression at 6 h, while P2Y5 showed higher expression at 6 and 24 h; regardless of the chicken line, PC chickens exhibited higher expression of P2X2, P2Y8, P2Y10, P2Y13, and P2Y14 when exposed to either group of infected chickens. In addition, MDV infection altered the expression of DDX5 in both WL and PC groups exposed to PC-infected birds only. However, irrespective of the source of exposure, BCL2 and ANGPTL4 showed higher expression in both WL and PC. The expression of STAT1A and STAT5A was influenced by time and breed, with major changes observed in STAT5A. CAT and SOD1 expression significantly increased in both WL and PC birds, regardless of the source of infection. GPX1 and GPX2 expression also increased in both WL and PC, although overall lower expression was observed in PC chickens at 24 h compared to 6 h. Our data suggest systemic changes in the host during early infection, indicated by the altered expression of PRs, DDX5, BCL2, ANGPTL4, and other regulatory genes during early MDV infection. The relative expression of these responses in PC and WL chickens suggests they may play a key role in their response to natural MDV infection in the lungs and long-term pathogenesis and survival. Full article
(This article belongs to the Special Issue Marek's Disease Virus)
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11 pages, 1523 KiB  
Article
Transovarial Transmission of Cell-Fusing Agent Virus in Naturally Infected Aedes aegypti Mosquitoes
by Dilip K. Nag and Kathryn J. Efner
Viruses 2024, 16(7), 1116; https://doi.org/10.3390/v16071116 - 11 Jul 2024
Cited by 1 | Viewed by 1897
Abstract
Mosquito-borne arboviruses include several pathogens that are responsible for many diseases of significant public health burden. Mosquitoes also host many insect-specific viruses that cannot replicate in vertebrate cells. These insect-specific viruses persist in nature predominantly via vertical transmission (VT), and they exhibit high [...] Read more.
Mosquito-borne arboviruses include several pathogens that are responsible for many diseases of significant public health burden. Mosquitoes also host many insect-specific viruses that cannot replicate in vertebrate cells. These insect-specific viruses persist in nature predominantly via vertical transmission (VT), and they exhibit high VT rates (VTRs). Cell-fusing agent virus (CFAV), an insect-specific orthoflavivirus, shows high VTRs in naturally infected mosquitoes but not in artificially infected mosquitoes. To determine whether the high VTRs are due to transovarial transmission, we investigated VT and ovary infection patterns in naturally CFAV-infected Aedes aegypti (Bangkok) mosquitoes. VT was monitored by detecting CFAV among the progeny by reverse-transcription polymerase chain reaction and ovary infection was determined by in situ hybridization using a virus-specific probe. We showed that in CFAV-positive mosquitoes, ovarian follicles were infected, suggesting that VT occurs by transovarial transmission in naturally infected mosquitoes. Additionally, mosquitoes harbored dormant, non-replicative CFAV that remained below the detection level. These results suggested that CFAV persists via VT in nature and has the potential to remain dormant in diapausing mosquitoes during unfavorable conditions. Understanding this VT mechanism is crucial for comprehending the persistence of insect-specific viruses (and potentially dual-host arboviruses) in their natural environment. Full article
(This article belongs to the Section Invertebrate Viruses)
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22 pages, 6191 KiB  
Article
Toward the Development of a Pan-Lyssavirus Vaccine
by Sabrine Ben Hamed, Jacob F. Myers, Anisha Chandwani, Christoph Wirblich, Drishya Kurup, Nir Paran and Matthias J. Schnell
Viruses 2024, 16(7), 1107; https://doi.org/10.3390/v16071107 - 10 Jul 2024
Viewed by 1990
Abstract
In addition to the rabies virus (RABV), 16 more lyssavirus species have been identified worldwide, causing a disease similar to RABV. Non-rabies-related human deaths have been described, but the number of cases is unknown, and the potential of such lyssaviruses causing human disease [...] Read more.
In addition to the rabies virus (RABV), 16 more lyssavirus species have been identified worldwide, causing a disease similar to RABV. Non-rabies-related human deaths have been described, but the number of cases is unknown, and the potential of such lyssaviruses causing human disease is unpredictable. The current rabies vaccine does not protect against divergent lyssaviruses such as Mokola virus (MOKV) or Lagos bat virus (LBV). Thus, a more broad pan-lyssavirus vaccine is needed. Here, we evaluate a novel lyssavirus vaccine with an attenuated RABV vector harboring a chimeric RABV glycoprotein (G) in which the antigenic site I of MOKV replaces the authentic site of rabies virus (RABVG-cAS1). The recombinant vaccine was utilized to immunize mice and analyze the immune response compared to homologous vaccines. Our findings indicate that the vaccine RABVG-cAS1 was immunogenic and induced high antibody titers against both RABVG and MOKVG. Challenge studies with different lyssaviruses showed that replacing a single antigenic site of RABV G with the corresponding site of MOKV G provides a significant improvement over the homologous RABV vaccine and protects against RABV, Irkut virus (IRKV), and MOKV. This strategy of epitope chimerization paves the way towards a pan-lyssavirus vaccine to safely combat the diseases caused by these viruses. Full article
(This article belongs to the Special Issue Advances in Rabies Research 2023)
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17 pages, 17312 KiB  
Article
The Structure of Spiroplasma Virus 4: Exploring the Capsid Diversity of the Microviridae
by Mario Mietzsch, Shweta Kailasan, Antonette Bennett, Paul Chipman, Bentley Fane, Juha T. Huiskonen, Ian N. Clarke and Robert McKenna
Viruses 2024, 16(7), 1103; https://doi.org/10.3390/v16071103 - 9 Jul 2024
Cited by 2 | Viewed by 1708
Abstract
Spiroplasma virus 4 (SpV4) is a bacteriophage of the Microviridae, which packages circular ssDNA within non-enveloped T = 1 icosahedral capsids. It infects spiroplasmas, which are known pathogens of honeybees. Here, the structure of the SpV4 virion is determined using cryo-electron microscopy [...] Read more.
Spiroplasma virus 4 (SpV4) is a bacteriophage of the Microviridae, which packages circular ssDNA within non-enveloped T = 1 icosahedral capsids. It infects spiroplasmas, which are known pathogens of honeybees. Here, the structure of the SpV4 virion is determined using cryo-electron microscopy to a resolution of 2.5 Å. A striking feature of the SpV4 capsid is the mushroom-like protrusions at the 3-fold axes, which is common among all members of the subfamily Gokushovirinae. While the function of the protrusion is currently unknown, this feature varies widely in this subfamily and is therefore possibly an adaptation for host recognition. Furthermore, on the interior of the SpV4 capsid, the location of DNA-binding protein VP8 was identified and shown to have low structural conservation to the capsids of other viruses in the family. The structural characterization of SpV4 will aid future studies analyzing the virus–host interaction, to understand disease mechanisms at a molecular level. Furthermore, the structural comparisons in this study, including a low-resolution structure of the chlamydia phage 2, provide an overview of the structural repertoire of the viruses in this family that infect various bacterial hosts, which in turn infect a wide range of animals and plants. Full article
(This article belongs to the Special Issue Structural Biology of Bacteriophages)
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22 pages, 2290 KiB  
Article
Evolution of RNA Viruses: Reasons for the Existence of Separate Plus, Minus, and Double-Strand Replication Strategies
by Hyunjin Park and Paul G. Higgs
Viruses 2024, 16(7), 1081; https://doi.org/10.3390/v16071081 - 5 Jul 2024
Viewed by 2622
Abstract
Plus, minus, and double-strand RNA viruses are all found in nature. We use computational models to study the relative success of these strategies. We consider translation, replication, and virion assembly inside one cell, and transmission of virions between cells. For viruses which do [...] Read more.
Plus, minus, and double-strand RNA viruses are all found in nature. We use computational models to study the relative success of these strategies. We consider translation, replication, and virion assembly inside one cell, and transmission of virions between cells. For viruses which do not incorporate a polymerase in the capsid, transmission of only plus strands is the default strategy because virions containing minus strands are not infectious. Packaging only plus strands has a significant advantage if the number of RNA strands produced per cell is larger than the number of capsids. In this case, by not packaging minus strands, the virus produces more plus-strand virions. Therefore, plus-strand viruses are selected at low multiplicity of infection. However, at high multiplicity of infection, it is preferable to package both strands because the additional minus virions produced are helpful when there are multiple infections per cell. The fact that plus-strand viruses are widespread while viruses that package both strands are not seen in nature suggests that RNA strands are indeed produced in excess over capsids, and that the multiplicity of infection is not sufficiently high to favor the production of both kinds of virions. For double-strand viruses, we show that it is advantageous to produce only plus strands from the double strand within the cell, as is observed in real viruses. The reason for the success of minus-strand viruses is more puzzling initially. For viruses that incorporate a polymerase in the virion, minus virions are infectious. However, this is not sufficient to explain the success of minus-strand viruses, because in this case, viruses that package both strands outcompete those that package only minus or only plus. Real minus-strand viruses make use of replicable strands that are coated by a nucleoprotein, and separate translatable plus strands that are uncoated. Here we show that when there are distinct replicable and translatable strands, minus-strand viruses are selected. Full article
(This article belongs to the Section General Virology)
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32 pages, 4747 KiB  
Article
Phage-Mediated Digestive Decolonization in a Gut-On-A-Chip Model: A Tale of Gut-Specific Bacterial Prosperity
by Brieuc Van Nieuwenhuyse, Maya Merabishvili, Nathalie Goeders, Kevin Vanneste, Bert Bogaerts, Mathieu de Jode, Joachim Ravau, Jeroen Wagemans, Leïla Belkhir and Dimitri Van der Linden
Viruses 2024, 16(7), 1047; https://doi.org/10.3390/v16071047 - 28 Jun 2024
Viewed by 1729
Abstract
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has [...] Read more.
Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has been postulated as a promising preventive intervention. However, previous attempts at such eradication using oral antibiotics or probiotics have led to discouraging results. Phage therapy, the therapeutic use of bacteriophage viruses, might represent a worthy alternative in this context. Taking inspiration from this clinical challenge, we built Gut-On-A-Chip (GOAC) models, which are tridimensional cell culture models mimicking a simplified gut section. These were used to better understand bacterial dynamics under phage pressure using two relevant species: Pseudomonas aeruginosa and Escherichia coli. Model mucus secretion was documented by ELISA assays. Bacterial dynamics assays were performed in GOAC triplicates monitored for 72 h under numerous conditions, such as pre-, per-, or post-bacterial timing of phage introduction, punctual versus continuous phage administration, and phage expression of mucus-binding properties. The potential genomic basis of bacterial phage resistance acquired in the model was investigated by variant sequencing. The bacterial “escape growth” rates under phage pressure were compared to static in vitro conditions. Our results suggest that there is specific bacterial prosperity in this model compared to other in vitro conditions. In E. coli assays, the introduction of a phage harboring unique mucus-binding properties could not shift this balance of power, contradicting previous findings in an in vivo mouse model and highlighting the key differences between these models. Genomic modifications were correlated with bacterial phage resistance acquisition in some but not all instances, suggesting that alternate ways are needed to evade phage predation, which warrants further investigation. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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20 pages, 1082 KiB  
Review
Engineered Resistance to Tobamoviruses
by John Peter Carr
Viruses 2024, 16(7), 1007; https://doi.org/10.3390/v16071007 - 22 Jun 2024
Cited by 2 | Viewed by 3241
Abstract
Tobacco mosaic virus (TMV) was the first virus to be studied in detail and, for many years, TMV and other tobamoviruses, particularly tomato mosaic virus (ToMV) and tobamoviruses infecting pepper (Capsicum spp.), were serious crop pathogens. By the end of the twentieth [...] Read more.
Tobacco mosaic virus (TMV) was the first virus to be studied in detail and, for many years, TMV and other tobamoviruses, particularly tomato mosaic virus (ToMV) and tobamoviruses infecting pepper (Capsicum spp.), were serious crop pathogens. By the end of the twentieth and for the first decade of the twenty-first century, tobamoviruses were under some degree of control due to introgression of resistance genes into commercial tomato and pepper lines. However, tobamoviruses remained important models for molecular biology, biotechnology and bio-nanotechnology. Recently, tobamoviruses have again become serious crop pathogens due to the advent of tomato brown rugose fruit virus, which overcomes tomato resistance against TMV and ToMV, and the slow but apparently inexorable worldwide spread of cucumber green mottle mosaic virus, which threatens all cucurbit crops. This review discusses a range of mainly molecular biology-based approaches for protecting crops against tobamoviruses. These include cross-protection (using mild tobamovirus strains to ‘immunize’ plants against severe strains), expressing viral gene products in transgenic plants to inhibit the viral infection cycle, inducing RNA silencing against tobamoviruses by expressing virus-derived RNA sequences in planta or by direct application of double-stranded RNA molecules to non-engineered plants, gene editing of host susceptibility factors, and the transfer and optimization of natural resistance genes. Full article
(This article belongs to the Special Issue Tobamoviruses: Molecular Aspects and Resistance Regulation—a Special Issue Commemorating 125 Years of Research on Tobamoviruses)
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15 pages, 2537 KiB  
Article
Bacteriophages and Green Synthesized Zinc Oxide Nanoparticles in Combination Are Efficient against Biofilm Formation of Pseudomonas aeruginosa
by Elaheh Alipour-Khezri, Amin Moqadami, Abolfazl Barzegar, Majid Mahdavi, Mikael Skurnik and Gholamreza Zarrini
Viruses 2024, 16(6), 897; https://doi.org/10.3390/v16060897 - 31 May 2024
Cited by 1 | Viewed by 1622
Abstract
Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas [...] Read more.
Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas aeruginosa, another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate P. aeruginosa biofilm alone or in combination with phages PB10 and PA19 was investigated. The P. aeruginosa cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP–phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group (p < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of P. aeruginosa was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene lasI. While the ZnO-NPs repressed the lasI gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells. Full article
(This article belongs to the Special Issue Bacteriophages and Biofilms 2.0)
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10 pages, 1191 KiB  
Article
Phage–Bacterial Interaction Alters Phenotypes Associated with Virulence in Acinetobacter baumannii
by Greater Kayode Oyejobi, Xiaoxu Zhang, Dongyan Xiong, Heng Xue, Mengjuan Shi, Hang Yang and Hongping Wei
Viruses 2024, 16(5), 743; https://doi.org/10.3390/v16050743 - 8 May 2024
Cited by 1 | Viewed by 1772
Abstract
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to [...] Read more.
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the in vitro virulence of priority 1 nosocomial pathogenic bacterium, Acinetobacter baumannii. By subjecting phage-resistant variant Ev5-WHG of A. baumannii WHG40004 to several in vitro virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in Acinetobacter baumannii. Full article
(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)
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12 pages, 1245 KiB  
Article
Host Barriers Limit Viral Spread in a Spillover Host: A Study of Deformed Wing Virus in the Bumblebee Bombus terrestris
by Tabea Streicher, Pina Brinker, Simon Tragust and Robert J. Paxton
Viruses 2024, 16(4), 607; https://doi.org/10.3390/v16040607 - 15 Apr 2024
Cited by 3 | Viewed by 2147
Abstract
The transmission of pathogens from reservoir to recipient host species, termed pathogen spillover, can profoundly impact plant, animal, and public health. However, why some pathogens lead to disease emergence in a novel species while others fail to establish or do not elicit disease [...] Read more.
The transmission of pathogens from reservoir to recipient host species, termed pathogen spillover, can profoundly impact plant, animal, and public health. However, why some pathogens lead to disease emergence in a novel species while others fail to establish or do not elicit disease is often poorly understood. There is strong evidence that deformed wing virus (DWV), an (+)ssRNA virus, spills over from its reservoir host, the honeybee Apis mellifera, into the bumblebee Bombus terrestris. However, the low impact of DWV on B. terrestris in laboratory experiments suggests host barriers to virus spread in this recipient host. To investigate potential host barriers, we followed the spread of DWV genotype B (DWV-B) through a host’s body using RT-PCR after experimental transmission to bumblebees in comparison to honeybees. Inoculation was per os, mimicking food-borne transmission, or by injection into the bee’s haemocoel, mimicking vector-based transmission. In honeybees, DWV-B was present in both honeybee faeces and haemolymph within 3 days of inoculation per os or by injection. In contrast, DWV-B was not detected in B. terrestris haemolymph after inoculation per os, suggesting a gut barrier that hinders DWV-B’s spread through the body of a B. terrestris. DWV-B was, however, detected in B. terrestris faeces after injection and feeding, albeit at a lower abundance than that observed for A. mellifera, suggesting that B. terrestris sheds less DWV-B than A. mellifera in faeces when infected. Barriers to viral spread in B. terrestris following oral infection may limit DWV’s impact on this spillover host and reduce its contribution to the community epidemiology of DWV. Full article
(This article belongs to the Section Invertebrate Viruses)
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32 pages, 407 KiB  
Article
The Medicinal Phage—Regulatory Roadmap for Phage Therapy under EU Pharmaceutical Legislation
by Timo Faltus
Viruses 2024, 16(3), 443; https://doi.org/10.3390/v16030443 - 12 Mar 2024
Cited by 15 | Viewed by 5416
Abstract
Bacteriophage therapy is a promising approach to treating bacterial infections. Research and development of bacteriophage therapy is intensifying due to the increase in antibiotic resistance and the faltering development of new antibiotics. Bacteriophage therapy uses bacteriophages (phages), i.e., prokaryotic viruses, to specifically target [...] Read more.
Bacteriophage therapy is a promising approach to treating bacterial infections. Research and development of bacteriophage therapy is intensifying due to the increase in antibiotic resistance and the faltering development of new antibiotics. Bacteriophage therapy uses bacteriophages (phages), i.e., prokaryotic viruses, to specifically target and kill pathogenic bacteria. The legal handling of this type of therapy raises several questions. These include whether phage therapeutics belong to a specially regulated class of medicinal products, and which legal framework should be followed with regard to the various technical ways in which phage therapeutics can be manufactured and administered. The article shows to which class of medicinal products phage therapeutics from wild type phages and from genetically modified (designer) phages do or do not belong. Furthermore, the article explains which legal framework is relevant for the manufacture and administration of phage therapeutics, which are manufactured in advance in a uniform, patient-independent manner, and for tailor-made patient-specific phage therapeutics. For the systematically coherent, successful translation of phage therapy, the article considers pharmaceutical law and related legal areas, such as genetic engineering law. Finally, the article shows how the planned legislative revisions of Directive 2001/83/EC and Regulation (EC) No 726/2004 may affect the legal future of phage therapy. Full article
(This article belongs to the Section Bacterial Viruses)
22 pages, 3968 KiB  
Article
Recommendations for Uniform Variant Calling of SARS-CoV-2 Genome Sequence across Bioinformatic Workflows
by Ryan Connor, Migun Shakya, David A. Yarmosh, Wolfgang Maier, Ross Martin, Rebecca Bradford, J. Rodney Brister, Patrick S. G. Chain, Courtney A. Copeland, Julia di Iulio, Bin Hu, Philip Ebert, Jonathan Gunti, Yumi Jin, Kenneth S. Katz, Andrey Kochergin, Tré LaRosa, Jiani Li, Po-E Li, Chien-Chi Lo, Sujatha Rashid, Evguenia S. Maiorova, Chunlin Xiao, Vadim Zalunin, Lisa Purcell and Kim D. Pruittadd Show full author list remove Hide full author list
Viruses 2024, 16(3), 430; https://doi.org/10.3390/v16030430 - 11 Mar 2024
Cited by 2 | Viewed by 15270
Abstract
Genomic sequencing of clinical samples to identify emerging variants of SARS-CoV-2 has been a key public health tool for curbing the spread of the virus. As a result, an unprecedented number of SARS-CoV-2 genomes were sequenced during the COVID-19 pandemic, which allowed for [...] Read more.
Genomic sequencing of clinical samples to identify emerging variants of SARS-CoV-2 has been a key public health tool for curbing the spread of the virus. As a result, an unprecedented number of SARS-CoV-2 genomes were sequenced during the COVID-19 pandemic, which allowed for rapid identification of genetic variants, enabling the timely design and testing of therapies and deployment of new vaccine formulations to combat the new variants. However, despite the technological advances of deep sequencing, the analysis of the raw sequence data generated globally is neither standardized nor consistent, leading to vastly disparate sequences that may impact identification of variants. Here, we show that for both Illumina and Oxford Nanopore sequencing platforms, downstream bioinformatic protocols used by industry, government, and academic groups resulted in different virus sequences from same sample. These bioinformatic workflows produced consensus genomes with differences in single nucleotide polymorphisms, inclusion and exclusion of insertions, and/or deletions, despite using the same raw sequence as input datasets. Here, we compared and characterized such discrepancies and propose a specific suite of parameters and protocols that should be adopted across the field. Consistent results from bioinformatic workflows are fundamental to SARS-CoV-2 and future pathogen surveillance efforts, including pandemic preparation, to allow for a data-driven and timely public health response. Full article
(This article belongs to the Special Issue Molecular and Computational Studies in Epidemiology and Evolution of Pandemic Virus)
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16 pages, 5599 KiB  
Article
Discovery of a Novel Antiviral Effect of the Restriction Factor SPOC1 against Human Cytomegalovirus
by Anna K. Kuderna, Anna Reichel, Julia Tillmanns, Maja Class, Myriam Scherer and Thomas Stamminger
Viruses 2024, 16(3), 363; https://doi.org/10.3390/v16030363 - 27 Feb 2024
Viewed by 1889
Abstract
The chromatin-remodeler SPOC1 (PHF13) is a transcriptional co-regulator and has been identified as a restriction factor against various viruses, including human cytomegalovirus (HCMV). For HCMV, SPOC1 was shown to block the onset of immediate-early (IE) gene expression under low multiplicities of infection (MOI). [...] Read more.
The chromatin-remodeler SPOC1 (PHF13) is a transcriptional co-regulator and has been identified as a restriction factor against various viruses, including human cytomegalovirus (HCMV). For HCMV, SPOC1 was shown to block the onset of immediate-early (IE) gene expression under low multiplicities of infection (MOI). Here, we demonstrate that SPOC1-mediated restriction of IE expression is neutralized by increasing viral titers. Interestingly, our study reveals that SPOC1 exerts an additional antiviral function beyond the IE phase of HCMV replication. Expression of SPOC1 under conditions of high MOI resulted in severely impaired viral DNA replication and viral particle release, which may be attributed to inefficient viral transcription. With the use of click chemistry, the localization of viral DNA was investigated at late time points after infection. Intriguingly, we detected a co-localization of SPOC1, RNA polymerase II S5P and polycomb repressor complex 2 (PRC2) components in close proximity to viral DNA in areas that are hypothesized to harbor viral transcription sites. We further identified the N-terminal domain of SPOC1 to be responsible for interaction with EZH2, a subunit of the PRC2 complex. With this study, we report a novel and potent antiviral function of SPOC1 against HCMV that is efficient even with unrestricted IE gene expression. Full article
(This article belongs to the Special Issue Molecular Biology of Human Cytomegalovirus)
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12 pages, 8282 KiB  
Commentary
Viroids, Satellite RNAs and Prions: Folding of Nucleic Acids and Misfolding of Proteins
by Gerhard Steger, Detlev Riesner and Stanley B. Prusiner
Viruses 2024, 16(3), 360; https://doi.org/10.3390/v16030360 - 26 Feb 2024
Cited by 2 | Viewed by 4198
Abstract
Theodor (“Ted”) Otto Diener (* 28 February 1921 in Zürich, Switzerland; † 28 March 2023 in Beltsville, MD, USA) pioneered research on viroids while working at the Plant Virology Laboratory, Agricultural Research Service, USDA, in Beltsville. He coined the name viroid and defined [...] Read more.
Theodor (“Ted”) Otto Diener (* 28 February 1921 in Zürich, Switzerland; † 28 March 2023 in Beltsville, MD, USA) pioneered research on viroids while working at the Plant Virology Laboratory, Agricultural Research Service, USDA, in Beltsville. He coined the name viroid and defined viroids’ important features like the infectivity of naked single-stranded RNA without protein-coding capacity. During scientific meetings in the 1970s and 1980s, viroids were often discussed at conferences together with other “subviral pathogens”. This term includes what are now called satellite RNAs and prions. Satellite RNAs depend on a helper virus and have linear or, in the case of virusoids, circular RNA genomes. Prions, proteinaceous infectious particles, are the agents of scrapie, kuru and some other diseases. Many satellite RNAs, like viroids, are non-coding and exert their function by thermodynamically or kinetically controlled folding, while prions are solely host-encoded proteins that cause disease by misfolding, aggregation and transmission of their conformations into infectious prion isoforms. In this memorial, we will recall the work of Ted Diener on subviral pathogens. Full article
(This article belongs to the Special Issue Viroids and Satellites and Their Vector Interactions—This Special Issue Is Dedicated to the Memory of Theodor O. Diener Who Discovered Viroids)
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12 pages, 969 KiB  
Article
Bivalent VSV Vectors Mediate Rapid and Potent Protection from Andes Virus Challenge in Hamsters
by Joshua Marceau, David Safronetz, Cynthia Martellaro, Andrea Marzi, Kyle Rosenke and Heinz Feldmann
Viruses 2024, 16(2), 279; https://doi.org/10.3390/v16020279 - 11 Feb 2024
Viewed by 2057
Abstract
Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human–human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters. Here, we utilized a promising [...] Read more.
Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human–human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters. Here, we utilized a promising vesicular stomatitis virus (VSV)-based vaccine to advance the approach for emergency applications. We compared monovalent and bivalent VSV vectors containing the Ebola virus (EBOV), glycoprotein (GP), and ANDV glycoprotein precursor (GPC) for protective efficacy in pre-, peri- and post-exposure immunization by the intraperitoneal and intranasal routes. Inclusion of the EBOV GP was based on its favorable immune cell targeting and the strong innate responses elicited by the VSV-EBOV vaccine. Our data indicates no difference of ANDV GPC expressing VSV vectors in pre-exposure immunization independent of route, but a potential benefit of the bivalent VSVs following peri- and post-exposure intraperitoneal vaccination. Full article
(This article belongs to the Special Issue Hantavirus Ecology, Epidemiology, and Disease, in Memory of Dr. Ho Wang Lee)
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18 pages, 3792 KiB  
Article
Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease
by Tabitha E. Hoornweg, Willem Schaftenaar, Victor P. M. G. Rutten and Cornelis A. M. de Haan
Viruses 2024, 16(2), 268; https://doi.org/10.3390/v16020268 - 8 Feb 2024
Cited by 1 | Viewed by 2404
Abstract
Elephant endotheliotropic herpesviruses (EEHVs), of which eleven (sub)species are currently distinguished, infect either Asian (Elephas maximus) or African elephants (Loxodonta species). While all adult elephants are latently infected with at least one EEHV (sub)species, young elephants, specifically those with low [...] Read more.
Elephant endotheliotropic herpesviruses (EEHVs), of which eleven (sub)species are currently distinguished, infect either Asian (Elephas maximus) or African elephants (Loxodonta species). While all adult elephants are latently infected with at least one EEHV (sub)species, young elephants, specifically those with low to non-detectable EEHV-specific antibody levels, may develop fatal hemorrhagic disease (EEHV-HD) upon infection. However, animals with high antibody levels against EEHV(1A) gB, an immunodominant antigen recognized by antibodies elicited against multiple (sub)species, may also occasionally succumb to EEHV-HD. To better define which animals are at risk of EEHV-HD, gB and gH/gL ELISAs were developed for each of the Asian elephant EEHV subspecies and assessed using 396 sera from 164 Asian elephants from European zoos. Antibody levels measured against gB of different (sub)species correlated strongly with one another, suggesting high cross-reactivity. Antibody levels against gH/gL of different subspecies were far less correlated and allowed differentiation between these (sub)species. Importantly, while high gB-specific antibody levels were detected in the sera of several EEHV-HD fatalities, all fatalities (n = 23) had low antibody levels against gH/gL of the subspecies causing disease. Overall, our data indicate that (sub)species-specific gH/gL ELISAs can be used to identify animals at risk of EEHV-HD when infected with a particular EEHV (sub)species. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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18 pages, 2290 KiB  
Technical Note
Robust Approaches to the Quantitative Analysis of Genome Formula Variation in Multipartite and Segmented Viruses
by Marcelle L. Johnson and Mark P. Zwart
Viruses 2024, 16(2), 270; https://doi.org/10.3390/v16020270 - 8 Feb 2024
Viewed by 1943
Abstract
When viruses have segmented genomes, the set of frequencies describing the abundance of segments is called the genome formula. The genome formula is often unbalanced and highly variable for both segmented and multipartite viruses. A growing number of studies are quantifying the genome [...] Read more.
When viruses have segmented genomes, the set of frequencies describing the abundance of segments is called the genome formula. The genome formula is often unbalanced and highly variable for both segmented and multipartite viruses. A growing number of studies are quantifying the genome formula to measure its effects on infection and to consider its ecological and evolutionary implications. Different approaches have been reported for analyzing genome formula data, including qualitative description, applying standard statistical tests such as ANOVA, and customized analyses. However, these approaches have different shortcomings, and test assumptions are often unmet, potentially leading to erroneous conclusions. Here, we address these challenges, leading to a threefold contribution. First, we propose a simple metric for analyzing genome formula variation: the genome formula distance. We describe the properties of this metric and provide a framework for understanding metric values. Second, we explain how this metric can be applied for different purposes, including testing for genome-formula differences and comparing observations to a reference genome formula value. Third, we re-analyze published data to illustrate the applications and weigh the evidence for previous conclusions. Our re-analysis of published datasets confirms many previous results but also provides evidence that the genome formula can be carried over from the inoculum to the virus population in a host. The simple procedures we propose contribute to the robust and accessible analysis of genome-formula data. Full article
(This article belongs to the Special Issue Plant Virus Epidemiology and Control 2023)
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19 pages, 3155 KiB  
Article
The Inovirus Pf4 Triggers Antiviral Responses and Disrupts the Proliferation of Airway Basal Epithelial Cells
by Medeea C. Popescu, Naomi L. Haddock, Elizabeth B. Burgener, Laura S. Rojas-Hernandez, Gernot Kaber, Aviv Hargil, Paul L. Bollyky and Carlos E. Milla
Viruses 2024, 16(1), 165; https://doi.org/10.3390/v16010165 - 22 Jan 2024
Cited by 2 | Viewed by 2282
Abstract
Background: The inovirus Pf4 is a lysogenic bacteriophage of Pseudomonas aeruginosa (Pa). People with Cystic Fibrosis (pwCF) experience chronic airway infection with Pa and a significant proportion have high numbers of Pf4 in their airway secretions. Given the known severe damage [...] Read more.
Background: The inovirus Pf4 is a lysogenic bacteriophage of Pseudomonas aeruginosa (Pa). People with Cystic Fibrosis (pwCF) experience chronic airway infection with Pa and a significant proportion have high numbers of Pf4 in their airway secretions. Given the known severe damage in the airways of Pa-infected pwCF, we hypothesized a high Pf4 burden can affect airway healing and inflammatory responses. In the airway, basal epithelial cells (BCs) are a multipotent stem cell population critical to epithelium homeostasis and repair. We sought to investigate the transcriptional responses of BCs under conditions that emulate infection with Pa and exposure to high Pf4 burden. Methods: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional assays. Results: We found that BCs internalized Pf4 and this elicits a strong antiviral response as well as neutrophil chemokine production. Further, we found that BCs that take up Pf4 demonstrate defective migration and proliferation. Conclusions: Our findings are highly suggestive of Pf4 playing a role in the pathogenicity of Pa in the airways. These findings provide additional evidence for the ability of inoviruses to interact with mammalian cells and disrupt cell function. Full article
(This article belongs to the Special Issue Inoviruses)
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18 pages, 32199 KiB  
Article
Partial Atomic Model of the Tailed Lactococcal Phage TP901-1 as Predicted by AlphaFold2: Revelations and Limitations
by Jennifer Mahony, Adeline Goulet, Douwe van Sinderen and Christian Cambillau
Viruses 2023, 15(12), 2440; https://doi.org/10.3390/v15122440 - 15 Dec 2023
Cited by 3 | Viewed by 3288
Abstract
Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phages). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. [...] Read more.
Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phages). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. Tailed phages possessing dsDNA genomes are the most abundant phages in the bacterial virosphere, particularly those with long, non-contractile tails. All tailed phages possess a nano-device at their tail tip that specifically recognizes and adheres to a suitable host cell surface receptor, being proteinaceous and/or saccharidic. Adhesion devices of tailed phages infecting Gram-positive bacteria are highly diverse and, for the majority, remain poorly understood. Their long, flexible, multi-domain-encompassing tail limits experimental approaches to determine their complete structure. We have previously shown that the recently developed protein structure prediction program AlphaFold2 can overcome this limitation by predicting the structures of phage adhesion devices with confidence. Here, we extend this approach and employ AlphaFold2 to determine the structure of a complete phage, the lactococcal P335 phage TP901-1. Herein we report the structures of its capsid and neck, its extended tail, and the complete adhesion device, the baseplate, which was previously partially determined using X-ray crystallography. Full article
(This article belongs to the Section Bacterial Viruses)
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38 pages, 2700 KiB  
Review
Evolving Horizons: Adenovirus Vectors’ Timeless Influence on Cancer, Gene Therapy and Vaccines
by Prasad D. Trivedi, Barry J. Byrne and Manuela Corti
Viruses 2023, 15(12), 2378; https://doi.org/10.3390/v15122378 - 3 Dec 2023
Cited by 20 | Viewed by 7966
Abstract
Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy [...] Read more.
Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy by altering the wild-type virus and making it replication-defective; specific viral genes can be removed and replaced with a segment that holds a therapeutic gene, and this vector can be used as delivery vehicle for tissue specific gene delivery. Modified conditionally replicative–oncolytic adenoviruses target tumors exclusively and have been studied in clinical trials extensively. This comprehensive review seeks to offer a summary of adenovirus vectors, exploring their characteristics, genetic enhancements, and diverse applications in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing cancer therapy and the latest breakthroughs in vaccine clinical trials for various diseases. Additionally, we tackle current challenges and future avenues for optimizing adenovirus vectors, promising to open new frontiers in the fields of cell and gene therapies. Full article
(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), 2nd Edition)
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16 pages, 2322 KiB  
Article
Enhanced Susceptibility to Tomato Chlorosis Virus (ToCV) in Hsp90- and Sgt1-Silenced Plants: Insights from Gene Expression Dynamics
by Irene Ontiveros, Noé Fernández-Pozo, Anna Esteve-Codina, Juan José López-Moya and Juan Antonio Díaz-Pendón
Viruses 2023, 15(12), 2370; https://doi.org/10.3390/v15122370 - 30 Nov 2023
Cited by 2 | Viewed by 2684
Abstract
The emerging whitefly-transmitted crinivirus tomato chlorosis virus (ToCV) causes substantial economic losses by inducing yellow leaf disorder in tomato crops. This study explores potential resistance mechanisms by examining early-stage molecular responses to ToCV. A time-course transcriptome analysis compared naïve, mock, and ToCV-infected plants [...] Read more.
The emerging whitefly-transmitted crinivirus tomato chlorosis virus (ToCV) causes substantial economic losses by inducing yellow leaf disorder in tomato crops. This study explores potential resistance mechanisms by examining early-stage molecular responses to ToCV. A time-course transcriptome analysis compared naïve, mock, and ToCV-infected plants at 2, 7, and 14 days post-infection (dpi). Gene expression changes were most notable at 2 and 14 dpi, likely corresponding to whitefly feeding and viral infection. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed key genes and pathways associated with ToCV infection, including those related to plant immunity, flavonoid and steroid biosynthesis, photosynthesis, and hormone signaling. Additionally, virus-derived small interfering RNAs (vsRNAs) originating from ToCV predominantly came from RNA2 and were 22 nucleotides in length. Furthermore, two genes involved in plant immunity, Hsp90 (heat shock protein 90) and its co-chaperone Sgt1 (suppressor of the G2 allele of Skp1) were targeted through viral-induced gene silencing (VIGS), showing a potential contribution to basal resistance against viral infections since their reduction correlated with increased ToCV accumulation. This study provides insights into tomato plant responses to ToCV, with potential implications for developing effective disease control strategies. Full article
(This article belongs to the Special Issue Plant Virus Resistance)
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24 pages, 3513 KiB  
Review
The Functional Implications of Broad Spectrum Bioactive Compounds Targeting RNA-Dependent RNA Polymerase (RdRp) in the Context of the COVID-19 Pandemic
by Brittany A. Comunale, Robin J. Larson, Erin Jackson-Ward, Aditi Singh, Frances L. Koback and Lilly D. Engineer
Viruses 2023, 15(12), 2316; https://doi.org/10.3390/v15122316 - 25 Nov 2023
Cited by 3 | Viewed by 2382
Abstract
Background: As long as COVID-19 endures, viral surface proteins will keep changing and new viral strains will emerge, rendering prior vaccines and treatments decreasingly effective. To provide durable targets for preventive and therapeutic agents, there is increasing interest in slowly mutating viral proteins, [...] Read more.
Background: As long as COVID-19 endures, viral surface proteins will keep changing and new viral strains will emerge, rendering prior vaccines and treatments decreasingly effective. To provide durable targets for preventive and therapeutic agents, there is increasing interest in slowly mutating viral proteins, including non-surface proteins like RdRp. Methods: A scoping review of studies was conducted describing RdRp in the context of COVID-19 through MEDLINE/PubMed and EMBASE. An iterative approach was used with input from content experts and three independent reviewers, focused on studies related to either RdRp activity inhibition or RdRp mechanisms against SARS-CoV-2. Results: Of the 205 records screened, 43 studies were included in the review. Twenty-five evaluated RdRp activity inhibition, and eighteen described RdRp mechanisms of existing drugs or compounds against SARS-CoV-2. In silico experiments suggested that RdRp inhibitors developed for other RNA viruses may be effective in disrupting SARS-CoV-2 replication, indicating a possible reduction of disease progression from current and future variants. In vitro, in vivo, and human clinical trial studies were largely consistent with these findings. Conclusions: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins. Full article
(This article belongs to the Special Issue Broad-Spectrum Antivirals and Interaction with Viruses)
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12 pages, 2187 KiB  
Article
A Robust Phenotypic High-Throughput Antiviral Assay for the Discovery of Rabies Virus Inhibitors
by Xinyu Wang, Winston Chiu, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Johan Neyts and Dirk Jochmans
Viruses 2023, 15(12), 2292; https://doi.org/10.3390/v15122292 - 23 Nov 2023
Cited by 1 | Viewed by 3028
Abstract
Rabies virus (RABV) causes severe neurological symptoms in mammals. The disease is almost inevitably lethal as soon as clinical symptoms appear. The use of rabies immunoglobulins (RIG) and vaccination in post-exposure prophylaxis (PEP) can provide efficient protection, but many people do not receive [...] Read more.
Rabies virus (RABV) causes severe neurological symptoms in mammals. The disease is almost inevitably lethal as soon as clinical symptoms appear. The use of rabies immunoglobulins (RIG) and vaccination in post-exposure prophylaxis (PEP) can provide efficient protection, but many people do not receive this treatment due to its high cost and/or limited availability. Highly potent small molecule antivirals are urgently needed to treat patients once symptoms develop. In this paper, we report on the development of a high-throughput phenotypic antiviral screening assay based on the infection of BHK-21 cells with a fluorescent reporter virus and high content imaging readout. The assay was used to screen a repurposing library of 3681 drugs (all had been studied in phase 1 clinical trials). From this series, salinomycin was found to selectively inhibit viral replication by blocking infection at the entry stage. This shows that a high-throughput assay enables the screening of large compound libraries for the purposes of identifying inhibitors of RABV replication. These can then be optimized through medicinal chemistry efforts and further developed into urgently needed drugs for the treatment of symptomatic rabies. Full article
(This article belongs to the Special Issue Rabies Virus: Treatment and Prevention)
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19 pages, 8713 KiB  
Article
An Inducible ESCRT-III Inhibition Tool to Control HIV-1 Budding
by Haiyan Wang, Benoit Gallet, Christine Moriscot, Mylène Pezet, Christine Chatellard, Jean-Philippe Kleman, Heinrich Göttlinger, Winfried Weissenhorn and Cécile Boscheron
Viruses 2023, 15(12), 2289; https://doi.org/10.3390/v15122289 - 22 Nov 2023
Cited by 1 | Viewed by 2132
Abstract
HIV-1 budding as well as many other cellular processes require the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. Understanding the architecture of the native ESCRT-III complex at HIV-1 budding sites is limited due to spatial resolution and transient ESCRT-III recruitment. Here, we [...] Read more.
HIV-1 budding as well as many other cellular processes require the Endosomal Sorting Complex Required for Transport (ESCRT) machinery. Understanding the architecture of the native ESCRT-III complex at HIV-1 budding sites is limited due to spatial resolution and transient ESCRT-III recruitment. Here, we developed a drug-inducible transient HIV-1 budding inhibitory tool to enhance the ESCRT-III lifetime at budding sites. We generated autocleavable CHMP2A, CHMP3, and CHMP4B fusion proteins with the hepatitis C virus NS3 protease. We characterized the CHMP-NS3 fusion proteins in the absence and presence of protease inhibitor Glecaprevir with regard to expression, stability, localization, and HIV-1 Gag VLP budding. Immunoblotting experiments revealed rapid and stable accumulation of CHMP-NS3 fusion proteins. Notably, upon drug administration, CHMP2A-NS3 and CHMP4B-NS3 fusion proteins substantially decrease VLP release while CHMP3-NS3 exerted no effect but synergized with CHMP2A-NS3. Localization studies demonstrated the relocalization of CHMP-NS3 fusion proteins to the plasma membrane, endosomes, and Gag VLP budding sites. Through the combined use of transmission electron microscopy and video-microscopy, we unveiled drug-dependent accumulation of CHMP2A-NS3 and CHMP4B-NS3, causing a delay in HIV-1 Gag-VLP release. Our findings provide novel insight into the functional consequences of inhibiting ESCRT-III during HIV-1 budding and establish new tools to decipher the role of ESCRT-III at HIV-1 budding sites and other ESCRT-catalyzed cellular processes. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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16 pages, 1742 KiB  
Article
The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection
by Daniela Cavallone, Eric David B. Ornos, Gabriele Ricco, Filippo Oliveri, Barbara Coco, Piero Colombatto, Laura De Rosa, Leslie Michelle M. Dalmacio, Ferruccio Bonino and Maurizia Rossana Brunetto
Viruses 2023, 15(11), 2257; https://doi.org/10.3390/v15112257 - 15 Nov 2023
Cited by 2 | Viewed by 1920
Abstract
miRNAs circulating in whole serum and HBsAg-particles are differentially expressed in chronic hepatitis B (CHB) and HBeAg-negative-HBV infection (ENI); their profiles are unknown in chronic hepatitis D (CHD). Serum- and HBsAg-associated miRNAs were analyzed in 75 subjects of 3 well-characterized groups (CHB 25, [...] Read more.
miRNAs circulating in whole serum and HBsAg-particles are differentially expressed in chronic hepatitis B (CHB) and HBeAg-negative-HBV infection (ENI); their profiles are unknown in chronic hepatitis D (CHD). Serum- and HBsAg-associated miRNAs were analyzed in 75 subjects of 3 well-characterized groups (CHB 25, CHD 25, ENI 25) using next-generation sequencing (NGS). Overall miRNA profiles were consonant in serum and HBsAg-particles but significantly different according to the presence of hepatitis independently of Hepatitis D Virus (HDV)-co-infection. Stringent (Bonferroni Correction < 0.001) differential expression analysis showed 39 miRNAs upregulated in CHB vs. ENI and 31 of them also in CHD vs. ENI. miRNA profiles were coincident in CHB and CHD with only miR-200a-3p upregulated in CHB. Three miRNAs (miR-625-3p, miR-142-5p, and miR-223-3p) involved in immune response were upregulated in ENI. All 3 hepatocellular miRNAs of MiR-B-Index (miR-122-5p, miR-99a-5p, miR-192-5p) were overexpressed in both CHB and CHD patients. In conclusion, CHD and CHB patients showed highly similar serum miRNA profiling that was significantly different from that of individuals with HBeAg-negative infection and without liver disease. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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13 pages, 1603 KiB  
Article
Identification of Host Factors for Rift Valley Fever Phlebovirus
by Velmurugan Balaraman, Sabarish V. Indran, Yonghai Li, David A. Meekins, Laxmi U. M. R. Jakkula, Heidi Liu, Micheal P. Hays, Jayme A. Souza-Neto, Natasha N. Gaudreault, Philip R. Hardwidge, William C. Wilson, Friedemann Weber and Juergen A. Richt
Viruses 2023, 15(11), 2251; https://doi.org/10.3390/v15112251 - 13 Nov 2023
Cited by 1 | Viewed by 2953
Abstract
Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV [...] Read more.
Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood. To identify the host factors or genes essential for RVFV replication, we conducted CRISPR-Cas9 knockout screening in human A549 cells. We then validated the putative genes using siRNA-mediated knock-downs and CRISPR-Cas9-mediated knock-out studies. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers were analyzed using plaque assay or TCID50 assay. We identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knock-downs revealed that silencing two genes (WDR7 and LRP1) significantly impaired RVFV replication. For further analysis, we focused on the WDR7 gene since the role of the LRP1 gene in RVFV replication was previously described in detail. WDR7 knockout A549 cell lines were generated and used to dissect the effect of WRD7 on a bunyavirus, RVFV, and an orthobunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects of WDR7 knockout cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level, WRD7 affected RVFV replication at a later phase of its replication cycle (24 h) when compared with the LACV replication, which was affected in an earlier replication phase (12 h). In summary, we identified WDR7 as an essential host factor for the replication of two different viruses, RVFV and LACV, both of which belong to the Bunyavirales order. Future studies will investigate the mechanistic role through which WDR7 facilitates phlebovirus replication. Full article
(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)
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12 pages, 2184 KiB  
Article
Nanoluciferase Reporter Zika Viruses as Tools for Assessing Infection Kinetics and Antibody Potency
by Yanqun Xu, Devin Vertrees, Yong He, Sanaz Momben-Abolfath, Xiaohong Li, Yambasu A. Brewah, Dorothy E. Scott, Krishnamurthy Konduru, Maria Rios and Evi B. Struble
Viruses 2023, 15(11), 2190; https://doi.org/10.3390/v15112190 - 31 Oct 2023
Cited by 4 | Viewed by 2107
Abstract
Zika virus (ZIKV) has become endemic in multiple tropical and subtropical regions and has the potential to become widespread in countries with limited prior exposure to this infection. One of the most concerning sequelae of ZIKV infection is the teratogenic effect on the [...] Read more.
Zika virus (ZIKV) has become endemic in multiple tropical and subtropical regions and has the potential to become widespread in countries with limited prior exposure to this infection. One of the most concerning sequelae of ZIKV infection is the teratogenic effect on the developing fetus, with the mechanisms of viral spread to and across the placenta remaining largely unknown. Although vaccine trials and prophylactic or therapeutic treatments are being studied, there are no approved treatments or vaccines for ZIKV. Appropriate tests, including potency and in vivo assays to assess the safety and efficacy of these modalities, can greatly aid both the research of the pathophysiology of the infection and the development of anti-ZIKV therapeutics. Building on previous work, we tested reporter ZIKV variants that express nanoluciferase in cell culture and in vivo assays. We found that these variants can propagate in cells shown to be susceptible to the widely used clinical isolate PRVABC59, including Vero and human placenta cell lines. When used in neutralization assays with bioluminescence as readout, these variants gave rise to neutralization curves similar to those produced by PRVABC59, while being better suited for performing high-throughput assays. In addition, the engineered reporter variants can be useful research tools when used in other in vitro and in vivo assays, as we illustrated in transcytosis experiments and a pilot study in guinea pigs. Full article
(This article belongs to the Special Issue Arbovirus Diagnostics)
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17 pages, 2446 KiB  
Article
Pteropus vampyrus TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
by Sarah van Tol, Adam Hage, Ricardo Rajsbaum and Alexander N. Freiberg
Viruses 2023, 15(11), 2147; https://doi.org/10.3390/v15112147 - 25 Oct 2023
Cited by 3 | Viewed by 2276
Abstract
Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the [...] Read more.
Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the mechanisms that facilitate bats’ tolerance. Tripartite motif proteins (TRIMs), a large family of E3-ubiquitin ligases, fine-tune innate antiviral immune responses, and two human TRIMs interact with Henipavirus proteins. We hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human cells, to promote tolerance. Here, we show that TRIM40 is an interferon-stimulated gene (ISG) in pteropodid but not human cells. Knockdown of bat TRIM40 increases gene expression of IFNβ, ISGs, and pro-inflammatory cytokines following poly(I:C) transfection. In Pteropus vampyrus, but not human cells, NiV induces TRIM40 expression within 16 h after infection, and knockdown of TRIM40 correlates with reduced NiV titers as compared to control cells. Bats may have evolved to express TRIM40 in response to viral infections to control immunopathogenesis. Full article
(This article belongs to the Special Issue TRIM Proteins in Antiviral Immunity and Virus Pathogenesis)
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13 pages, 1217 KiB  
Review
Diversity and Current Classification of dsRNA Bacteriophages
by Sari Mäntynen, Meri M. Salomaa and Minna M. Poranen
Viruses 2023, 15(11), 2154; https://doi.org/10.3390/v15112154 - 25 Oct 2023
Cited by 5 | Viewed by 3315
Abstract
Half a century has passed since the discovery of Pseudomonas phage phi6, the first enveloped dsRNA bacteriophage to be isolated. It remained the sole known dsRNA phage for a quarter of a century and the only recognised member of the Cystoviridae family until [...] Read more.
Half a century has passed since the discovery of Pseudomonas phage phi6, the first enveloped dsRNA bacteriophage to be isolated. It remained the sole known dsRNA phage for a quarter of a century and the only recognised member of the Cystoviridae family until the year 2018. After the initial discovery of phi6, additional dsRNA phages have been isolated from globally distant locations and identified in metatranscriptomic datasets, suggesting that this virus type is more ubiquitous in nature than previously acknowledged. Most identified dsRNA phages infect Pseudomonas strains and utilise either pilus or lipopolysaccharide components of the host as the primary receptor. In addition to the receptor-mediated strictly lytic lifestyle, an alternative persistent infection strategy has been described for some dsRNA phages. To date, complete genome sequences of fourteen dsRNA phage isolates are available. Despite the high sequence diversity, similar sets of genes can typically be found in the genomes of dsRNA phages, suggesting shared evolutionary trajectories. This review provides a brief overview of the recognised members of the Cystoviridae virus family and related dsRNA phage isolates, outlines the current classification of dsRNA phages, and discusses their relationships with eukaryotic RNA viruses. Full article
(This article belongs to the Special Issue Discovery, Classification, and Early Research on the Lipid-Containing, Double-Stranded RNA Bacteriophage φ6)
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11 pages, 1559 KiB  
Brief Report
A Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Protect Pigs against a Virulent CSFV Challenge
by Ediane Silva, Elizabeth Medina-Ramirez, Selvaraj Pavulraj, Douglas P. Gladue, Manuel Borca and Shafiqul I. Chowdhury
Viruses 2023, 15(11), 2143; https://doi.org/10.3390/v15112143 - 25 Oct 2023
Cited by 1 | Viewed by 1901
Abstract
Classical swine fever (CSF) remains one of the most economically significant viral diseases affecting domestic pigs and wild boars worldwide. To develop a safe and effective vaccine against CSF, we have constructed a triple gene-deleted pseudorabies virus (PRVtmv)-vectored bivalent subunit vaccine against porcine [...] Read more.
Classical swine fever (CSF) remains one of the most economically significant viral diseases affecting domestic pigs and wild boars worldwide. To develop a safe and effective vaccine against CSF, we have constructed a triple gene-deleted pseudorabies virus (PRVtmv)-vectored bivalent subunit vaccine against porcine circovirus type 2b (PCV2b) and CSFV (PRVtmv+). In this study, we determined the protective efficacy of the PRVtmv+ against virulent CSFV challenge in pigs. The results revealed that the sham-vaccinated control group pigs developed severe CSFV-specific clinical signs characterized by pyrexia and diarrhea, and became moribund on or before the seventh day post challenge (dpc). However, the PRVtmv+-vaccinated pigs survived until the day of euthanasia at 21 dpc. A few vaccinated pigs showed transient diarrhea but recovered within a day or two. One pig had a low-grade fever for a day but recovered. The sham-vaccinated control group pigs had a high level of viremia, severe lymphocytopenia, and thrombocytopenia. In contrast, the vaccinated pigs had a low–moderate degree of lymphocytopenia and thrombocytopenia on four dpc, but recovered by seven dpc. Based on the gross pathology, none of the vaccinated pigs had any CSFV-specific lesions. Therefore, our results demonstrated that the PRVtmv+ vaccinated pigs are protected against virulent CSFV challenge. Full article
(This article belongs to the Special Issue Strategies for Preventing Viral Diseases of Domestic Animals)
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31 pages, 1731 KiB  
Review
Polyomavirus Wakes Up and Chooses Neurovirulence
by Arrienne B. Butic, Samantha A. Spencer, Shareef K. Shaheen and Aron E. Lukacher
Viruses 2023, 15(10), 2112; https://doi.org/10.3390/v15102112 - 18 Oct 2023
Cited by 7 | Viewed by 4165
Abstract
JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies [...] Read more.
JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease. Full article
(This article belongs to the Special Issue Neurotropic Viral Pathogens)
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14 pages, 2581 KiB  
Article
Small Heat Shock Protein (sHsp22.98) from Trialeurodes vaporariorum Plays Important Role in Apple Scar Skin Viroid Transmission
by Savita Chaudhary, Vijayanandraj Selvaraj, Preshika Awasthi, Swati Bhuria, Rituraj Purohit, Surender Kumar and Vipin Hallan
Viruses 2023, 15(10), 2069; https://doi.org/10.3390/v15102069 - 9 Oct 2023
Cited by 3 | Viewed by 4645
Abstract
Trialeurodes vaporariorum, commonly known as the greenhouse whitefly, severely infests important crops and serves as a vector for apple scar skin viroid (ASSVd). This vector-mediated transmission may cause the spread of infection to other herbaceous crops. For effective management of ASSVd, it is [...] Read more.
Trialeurodes vaporariorum, commonly known as the greenhouse whitefly, severely infests important crops and serves as a vector for apple scar skin viroid (ASSVd). This vector-mediated transmission may cause the spread of infection to other herbaceous crops. For effective management of ASSVd, it is important to explore the whitefly’s proteins, which interact with ASSVd RNA and are thereby involved in its transmission. In this study, it was found that a small heat shock protein (sHsp) from T. vaporariorum, which is expressed under stress, binds to ASSVd RNA. The sHsp gene is 606 bp in length and encodes for 202 amino acids, with a molecular weight of 22.98 kDa and an isoelectric point of 8.95. Intermolecular interaction was confirmed through in silico analysis, using electrophoretic mobility shift assays (EMSAs) and northwestern assays. The sHsp22.98 protein was found to exist in both monomeric and dimeric forms, and both forms showed strong binding to ASSVd RNA. To investigate the role of sHsp22.98 during ASSVd infection, transient silencing of sHsp22.98 was conducted, using a tobacco rattle virus (TRV)-based virus-induced gene silencing system. The sHsp22.98-silenced whiteflies showed an approximate 50% decrease in ASSVd transmission. These results suggest that sHsp22.98 from T. vaporariorum is associated with viroid RNA and plays a significant role in transmission. Full article
(This article belongs to the Special Issue Viroids and Satellites and Their Vector Interactions—This Special Issue Is Dedicated to the Memory of Theodor O. Diener Who Discovered Viroids)
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20 pages, 12369 KiB  
Article
Structure of Vibrio Phage XM1, a Simple Contractile DNA Injection Machine
by Zhiqing Wang, Andrei Fokine, Xinwu Guo, Wen Jiang, Michael G. Rossmann, Richard J. Kuhn, Zhu-Hua Luo and Thomas Klose
Viruses 2023, 15(8), 1673; https://doi.org/10.3390/v15081673 - 31 Jul 2023
Cited by 12 | Viewed by 2535
Abstract
Antibiotic resistance poses a growing risk to public health, requiring new tools to combat pathogenic bacteria. Contractile injection systems, including bacteriophage tails, pyocins, and bacterial type VI secretion systems, can efficiently penetrate cell envelopes and become potential antibacterial agents. Bacteriophage XM1 is a [...] Read more.
Antibiotic resistance poses a growing risk to public health, requiring new tools to combat pathogenic bacteria. Contractile injection systems, including bacteriophage tails, pyocins, and bacterial type VI secretion systems, can efficiently penetrate cell envelopes and become potential antibacterial agents. Bacteriophage XM1 is a dsDNA virus belonging to the Myoviridae family and infecting Vibrio bacteria. The XM1 virion, made of 18 different proteins, consists of an icosahedral head and a contractile tail, terminated with a baseplate. Here, we report cryo-EM reconstructions of all components of the XM1 virion and describe the atomic structures of 14 XM1 proteins. The XM1 baseplate is composed of a central hub surrounded by six wedge modules to which twelve spikes are attached. The XM1 tail contains a fewer number of smaller proteins compared to other reported phage baseplates, depicting the minimum requirements for building an effective cell-envelope-penetrating machine. We describe the tail sheath structure in the pre-infection and post-infection states and its conformational changes during infection. In addition, we report, for the first time, the in situ structure of the phage neck region to near-atomic resolution. Based on these structures, we propose mechanisms of virus assembly and infection. Full article
(This article belongs to the Special Issue Phage Structural Biology)
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13 pages, 2787 KiB  
Article
Apis mellifera Solinvivirus-1, a Novel Honey Bee Virus That Remained Undetected for over a Decade, Is Widespread in the USA
by Eugene V. Ryabov, Anthony J. Nearman, Ashrafun Nessa, Kyle Grubbs, Benjamin Sallmann, Rachel Fahey, Mikayla E. Wilson, Karen D. Rennich, Nathalie Steinhauer, Anne Marie Fauvel, Yanping Chen, Jay D. Evans and Dennis vanEngelsdorp
Viruses 2023, 15(7), 1597; https://doi.org/10.3390/v15071597 - 21 Jul 2023
Cited by 5 | Viewed by 5025
Abstract
A metagenomic analysis of the virome of honey bees (Apis mellifera) from an apiary with high rates of unexplained colony losses identified a novel RNA virus. The virus, which was named Apis mellifera solinvivirus 1 (AmSV1), contains a 10.6 kb positive-strand [...] Read more.
A metagenomic analysis of the virome of honey bees (Apis mellifera) from an apiary with high rates of unexplained colony losses identified a novel RNA virus. The virus, which was named Apis mellifera solinvivirus 1 (AmSV1), contains a 10.6 kb positive-strand genomic RNA with a single ORF coding for a polyprotein with the protease, helicase, and RNA-dependent RNA polymerase domains, as well as a single jelly-roll structural protein domain, showing highest similarity with viruses in the family Solinviviridae. The injection of honey bee pupae with AmSV1 preparation showed an increase in virus titer and the accumulation of the negative-strand of AmSV1 RNA 3 days after injection, indicating the replication of AmSV1. In the infected worker bees, AmSV1 was present in heads, thoraxes, and abdomens, indicating that this virus causes systemic infection. An analysis of the geographic and historic distribution of AmSV1, using over 900 apiary samples collected across the United States, showed AmSV1 presence since at least 2010. In the year 2021, AmSV1 was detected in 10.45% of apiaries (95%CI: 8.41–12.79%), mostly sampled in June and July in Northwestern and Northeastern United States. The diagnostic methods and information on the AmSV1 distribution will be used to investigate the connection of AmSV1 to honey bee colony losses. Full article
(This article belongs to the Section Invertebrate Viruses)
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