Viruses

6 pages, 670 KiB

Open AccessOpinion

Rogueing or Rescuing? A Potential New Management Approach for Roses Infected with Rose Rosette Virus

by Caleb Paslay and Akhtar Ali

Viruses 2025, 17(6), 829; https://doi.org/10.3390/v17060829 (registering DOI) - 8 Jun 2025

Roses (Rosa spp.) are among the most economically and culturally significant flowering plants worldwide. However, rose cultivation faces a critical threat from rose rosette disease (RRD), which is caused by Emaravirus rosae (rose rosette virus, RRV), a negative-sense RNA virus transmitted by [...] Read more.

Roses (Rosa spp.) are among the most economically and culturally significant flowering plants worldwide. However, rose cultivation faces a critical threat from rose rosette disease (RRD), which is caused by Emaravirus rosae (rose rosette virus, RRV), a negative-sense RNA virus transmitted by the eriophyid mite Phyllocoptes fructiphilus. Current RRD management strategies mainly depend on the complete removal (rogueing) of symptomatic plants, which are effective but adds high economic and aesthetic costs. During our field and laboratory observations from 2023 to 2024, we documented that RRV often remains localized to a single cane for extended periods of time (up to 80 days) in one variety before systemic spread to other canes of the same plant. This discovery supports a proposed “rescue hypothesis”, suggesting that early pruning of symptomatic canes may prevent full-plant infection and serve as a viable alternative to rogueing under specific conditions. While preliminary, our findings offer a potentially cost-effective, less destructive management strategy. However, further research is needed to validate this hypothesis and inform integrated disease management practices are established for effective control of RRD. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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25 pages, 7711 KiB

Open AccessArticle

Synergizing Attribute-Guided Latent Space Exploration (AGLSE) with Classical Molecular Simulations to Design Potent Pep-Magnet Peptide Inhibitors to Abrogate SARS-CoV-2 Host Cell Entry

by Farhan Ullah, Aobo Xiao, Shahid Ullah, Na Yang, Min Lei, Liang Chen and Sheng Wang

Viruses 2025, 17(6), 828; https://doi.org/10.3390/v17060828 (registering DOI) - 7 Jun 2025

Abstract

The COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evoked a worldwide pandemic. Even though vaccines have been developed on an enormous scale, but due to regular mutations in the viral gene and the emergence of new strains could [...] Read more.

The COVID-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evoked a worldwide pandemic. Even though vaccines have been developed on an enormous scale, but due to regular mutations in the viral gene and the emergence of new strains could pose a more significant problem for the population. Therefore, new treatments are always necessary to combat future pandemics. Utilizing an antiviral peptide as a model biomolecule, we trained a generative deep learning algorithm on a database of known antiviral peptides to design novel peptide sequences with antiviral activity. Using artificial intelligence (AI), specifically variational autoencoders (VAE) and Wasserstein autoencoders (WAE), we were able to generate a latent space plot that can be surveyed for peptides with known properties and interpolated across a predictive vector between two defined points to identify novel peptides that exhibit dose-responsive antiviral activity. Two hundred peptide sequences were generated from the trained latent space and the top peptides were subjected to a molecular docking study. The docking analysis revealed that the top four peptides (MSK-1, MSK-2, MSK-3, and MSK-4) exhibited the strongest binding affinity, with docking scores of −106.4, −126.2, −125.7, and −127.8, respectively. Molecular dynamics simulations lasting 500 ns were performed to assess their stability and binding interactions. Further analyses, including MMGBSA, RMSD, RMSF, and hydrogen bond analysis, confirmed the stability and strong binding interactions of the peptide–protein complexes, suggesting that MSK-4 is a promising therapeutic agent for further development. We believe that the peptides generated through AI and MD simulations in the current study could be potential inhibitors in natural systems that can be utilized in designing therapeutic strategies against SARS-CoV-2. Full article

(This article belongs to the Special Issue Harnessing AI and Machine Learning for Antiviral Development)

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12 pages, 1591 KiB

Open AccessCommunication

Myricetin Restricts the Syncytial Development Triggered by Nipah Virus Envelope Glycoproteins In Vitro

by Ananda Murali Rayapati, Chanda Chandrasekhar, Sudarsana Poojari and Bhadra Murthy Vemulapati

Viruses 2025, 17(6), 827; https://doi.org/10.3390/v17060827 (registering DOI) - 7 Jun 2025

Abstract

Background and Objectives: Myricetin, a flavonoid compound, was demonstrated to effectively arrest the cell-to-cell fusion and syncytial development triggered by Nipah virus (NiV) fusion (F) and attachment (G) envelope glycoproteins in vitro involving two permissive mammalian cell lines. Methods: Time-of-addition assays were [...] Read more.

Background and Objectives: Myricetin, a flavonoid compound, was demonstrated to effectively arrest the cell-to-cell fusion and syncytial development triggered by Nipah virus (NiV) fusion (F) and attachment (G) envelope glycoproteins in vitro involving two permissive mammalian cell lines. Methods: Time-of-addition assays were carried out using codon-optimized NiV wild type (WT) F and G plasmids followed by a challenge with the addition of myricetin 1 h and 6 h post-transfection in HEK 293T and Vero cells. Results: Upon evaluating different myricetin concentrations, it was determined that a 100 μM concentration of myricetin effectively inhibited 64–80% of syncytia in HEK and Vero cells. Interpretation & conclusions: In this study, we concluded that myricetin mitigated the syncytial development in HEK and Vero cell lines. Given the flavonoid attributes of myricetin which is widely present in fruits, vegetables, tea, and wine, it may be regarded as a phytonutrient and a safer antiviral alternative against Nipah virus infections. Due to the BSL-4 nature of the virus, further research involving live virus culture is necessary to confirm myricetin as a potential antiviral compound for the mitigation of pathological effects of NiV infections. Full article

(This article belongs to the Section General Virology)

19 pages, 7764 KiB

Open AccessArticle

Binding Specificity and Oligomerization of TSWV N Protein in the Western Flower Thrips, Frankliniella occidentalis

by Falguni Khan, Eticha Abdisa, Niayesh Shahmohammadi and Yonggyun Kim

Viruses 2025, 17(6), 826; https://doi.org/10.3390/v17060826 (registering DOI) - 7 Jun 2025

Abstract

Tomato spotted wilt virus (TSWV) is a highly destructive plant pathogen and transmitted by several thrips including the western flower thrips, Frankliniella occidentalis. A structural N protein encoded in the viral genome represents the nucleocapsid protein by binding to the viral RNA [...] Read more.

Tomato spotted wilt virus (TSWV) is a highly destructive plant pathogen and transmitted by several thrips including the western flower thrips, Frankliniella occidentalis. A structural N protein encoded in the viral genome represents the nucleocapsid protein by binding to the viral RNA genome. However, it remains unknown how the RNA-binding protein specifically interacts with the viral RNA from host RNAs in the target cells. To study the molecular basis of N function, we produced the protein in Escherichia coli and the resulting purified recombinant protein was used to investigate the protein–RNA interactions. The recombinant N protein migrated on agarose gel to the anode in the electric field due to its high basic isoelectric point. This electrostatic property led N protein to bind to DNA as well as RNA. It also bound to both single-stranded (ssRNA) and double-stranded RNA (dsRNA). However, when the total RNA was extracted from plant tissues collected from TSWV-infected host, the RNA extract using the recombinant N protein was much richer in the TSWV genome compared to that without the protein. To investigate the specificity of N protein to ssRNA, the three-dimensional structure was predicted using the AlphaFold program and showed its trimeric oligomerization with the binding pocket for ssRNA. This was supported by the differential susceptibility of N protein with ssRNA and dsRNA against RNase attack. Furthermore, a thermal shift assay to analyze the RNA and protein interaction showed that ssRNA strongly interacted with N protein compared to dsRNA. In addition, the N gene was expressed along with the multiplication of the viral RNA genome segments from the segment-specific fluorescence in situ hybridization analysis in different tissues during different developmental stages of the virus-infected F. occidentalis. These results suggest that the functional trimeric N proteins bind to the viral RNA to form a basic nucleocapsid structure at a specific virus-replicating compartment within the host cells. Full article

(This article belongs to the Special Issue Molecular Virus-Insect Interactions, 2nd Edition)

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15 pages, 773 KiB

Open AccessReview

Modulation of Plant Interactions with Whitefly and Whitefly-Borne Viruses by Salicylic Acid Signaling Pathway: A Review

by Shi-Xing Zhao, Su-Dan Wang, Yin-Quan Liu and Li-Long Pan

Viruses 2025, 17(6), 825; https://doi.org/10.3390/v17060825 (registering DOI) - 7 Jun 2025

Abstract

Whiteflies of the Bemisia tabaci complex, along with the plant viruses they transmit, pose significant challenges to crop production worldwide. Upon infestation or infection, intimate interactions occur between plant hosts and these pests, influencing the spread and severity of pest-related epidemics in natural [...] Read more.

Whiteflies of the Bemisia tabaci complex, along with the plant viruses they transmit, pose significant challenges to crop production worldwide. Upon infestation or infection, intimate interactions occur between plant hosts and these pests, influencing the spread and severity of pest-related epidemics in natural and agricultural ecosystems. This review explores the role of the salicylic acid (SA) signaling pathway, an essential component of plant defense, in modulating plant interactions with whiteflies and whitefly-borne viruses. We first outline the biosynthesis and signal transduction of SA. We then analyze how whitefly infestation activates the SA signaling pathway and how this defense response affects whitefly performance and preference. Next, we explore the interactions between the SA signaling pathway and whitefly-borne plant viruses, especially begomoviruses, which often activate and manipulate this pathway. We also examine how the SA signaling pathway influences plant–whitefly–virus tripartite interactions, highlighting the significant role of this defense pathway in whitefly-induced changes in plant–virus interactions and virus-induced changes in plant–whitefly interactions. Finally, we identify key areas for future research to further unravel the complexities of plant interactions with whiteflies and whitefly-borne viruses. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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18 pages, 2815 KiB

Open AccessArticle

The Involvement of MGF505 Genes in the Long-Term Persistence of the African Swine Fever Virus in Gastropods

by Sona Hakobyan, Nane Bayramyan, Zaven Karalyan, Roza Izmailyan, Aida Avetisyan, Arpine Poghosyan, Elina Arakelova, Tigranuhi Vardanyan and Hranush Avagyan

Viruses 2025, 17(6), 824; https://doi.org/10.3390/v17060824 (registering DOI) - 7 Jun 2025

Abstract

African swine fever virus (ASFV), a highly contagious and lethal virus affecting domestic and wild pigs, has raised global concerns due to its continued spread across Europe and Asia. While traditional transmission pathways involve suids and soft ticks, this study investigates the potential [...] Read more.

African swine fever virus (ASFV), a highly contagious and lethal virus affecting domestic and wild pigs, has raised global concerns due to its continued spread across Europe and Asia. While traditional transmission pathways involve suids and soft ticks, this study investigates the potential role of freshwater gastropods as environmental reservoirs capable of sustaining ASFV. We analysed ASFV survival in ten gastropod species after long-term co-incubation with the virus. Viral transcriptional activity, particularly of the late gene B646L and members of the multigene family MGF505, was evaluated in snail faeces up to nine weeks post-infection. Results revealed that several gastropods, including Melanoides tuberculata, Tarebia granifera, Physa fontinalis, and Pomacea bridgesii, support long-term persistence of ASFV, accompanied by increased MGF505 gene expression. Notably, the simultaneous activation of MGF5052R and MGF50511R significantly correlated with higher B646L expression and extended viral survival, suggesting a functional role in ASFV maintenance. Conversely, antiviral (AV) activity assays showed that some gastropod faeces reduced replication of the unrelated Influenza virus, hinting at induced host defences. A negative correlation was observed between AV activity and the expression of MGF505 2R/11R, implying that ASFV may suppress antiviral responses to facilitate persistence. These findings suggest that certain gastropods may serve as overlooked environmental hosts, contributing to ASFV epidemiology via long term viral shedding. Further research is needed to clarify the mechanisms underlying ASFV–host interactions and to assess the ecological and epidemiological implications of gastropods in ASFV transmission cycles. Full article

(This article belongs to the Section Animal Viruses)

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11 pages, 4768 KiB

Open AccessArticle

Identification of a Conserved Linear Epitope on the p54 Protein of African Swine Fever Virus

by Kuijing He, Yue Wu, Zhipeng Su, Yue Zeng, Guishan Ye, Qi Wu, Long Li and Anding Zhang

Viruses 2025, 17(6), 823; https://doi.org/10.3390/v17060823 (registering DOI) - 7 Jun 2025

Abstract

African swine fever virus (ASFV) is a highly virulent pathogen that causes nearly 100% mortality in acute infections and poses persistent risks. Effective containment of ASFV outbreaks requires rapid and reliable diagnostic tools. The p54 protein, a key structural component of ASFV, has [...] Read more.

African swine fever virus (ASFV) is a highly virulent pathogen that causes nearly 100% mortality in acute infections and poses persistent risks. Effective containment of ASFV outbreaks requires rapid and reliable diagnostic tools. The p54 protein, a key structural component of ASFV, has emerged as an important target for serological detection. Herein, the recombinant p54 protein (amino acids 53–184) was expressed in Escherichia coli, and three mouse monoclonal antibodies (mAbs) (IgG1/kappa subtype) were developed. Among these mAbs, the mAb 1F9 specifically recognized the B-cell epitope ⁶⁶IQFINPYQDQQ⁷⁶, which is conserved across different genotypes of ASFV, suggesting that the epitope may serve as a valuable target for serological detection of ASFV. Structural modeling analysis revealed that this epitope is surface-exposed on the p54 protein, with ⁶⁷Gln and ⁶⁸Phe identified as critical residues for 1F9 binding. Moreover, a blocking ELISA based on the mAb 1F9 was established for detecting ASFV-specific antibodies in clinical serum samples, achieving a coincidence rate exceeding 95%. These findings demonstrate that mAb 1F9, targeting a conserved and accessible region of p54, represents a valuable tool for ASFV serodiagnosis, surveillance, and outbreak management. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 503 KiB

Open AccessArticle

Steroid Pulse Therapy Leads to Secondary Infections and Poor Outcomes in Patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Intensive Care Units: A Retrospective Cohort Study

by Katsuhiro Nakagawa, Shingo Ihara, Junko Yamaguchi, Tsukasa Kuwana and Kosaku Kinoshita

Viruses 2025, 17(6), 822; https://doi.org/10.3390/v17060822 - 6 Jun 2025

Abstract

The efficacy of steroid pulse therapy for treating severe coronavirus disease (COVID-19) pneumonia remains unclear. This study aimed to determine the efficacy of steroid pulse therapy for severe COVID-19 pneumonia in patients who did not respond to conventional therapy, including steroids. We included [...] Read more.

The efficacy of steroid pulse therapy for treating severe coronavirus disease (COVID-19) pneumonia remains unclear. This study aimed to determine the efficacy of steroid pulse therapy for severe COVID-19 pneumonia in patients who did not respond to conventional therapy, including steroids. We included 76 patients with severe COVID-19 pneumonia treated with steroids in this single-facility retrospective observational study. Severe COVID-19 pneumonia was defined as requiring high-concentration oxygen administration (oxygen mask with reservoir mask (RM) > 6 L/min), high-flow nasal cannula oxygen therapy, or ventilatory support for respiratory control. The patient characteristics at admission and changes in them over time were examined in (a) a survival vs. death group, and (b) a steroid pulse vs. non-steroid pulse therapy group. Steroid pulse therapy significantly improved the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen just after the therapy and after one week of therapy, but had no effect on the sequential organ failure assessment scores over time. Multivariate logistic regression analyses showed that remdesivir use was associated with better survival outcomes, while steroid pulse therapy was associated with poor outcomes. In conclusion, steroid pulse therapy did not improve the prognosis of patients with severe COVID-19 pneumonia any more effectively than conventional steroid therapy. Full article

(This article belongs to the Special Issue COVID-19 and Pneumonia, 3rd Edition)

20 pages, 2817 KiB

Open AccessArticle

A Versatile Reporter Platform for Evaluating HDR- and NHEJ-Based Genome Editing in Airway Epithelial Cell Cultures Using an rAAV Vector

by Soo Yeun Park, Zehua Feng, Xiujuan Zhang, Yinghua Tang, Donovan Richart, Kai E. Vorhies, Jianming Qiu, John F. Engelhardt and Ziying Yan

Viruses 2025, 17(6), 821; https://doi.org/10.3390/v17060821 - 6 Jun 2025

Abstract

Therapeutic gene editing strategies utilize endogenous DNA repair pathways—nonhomologous end joining (NHEJ) or homology-directed repair (HDR)—to introduce targeted genomic modifications. Because HDR is restricted to dividing cells, whereas NHEJ functions in both dividing and non-dividing cells, NHEJ-based approaches are better suited for in [...] Read more.

Therapeutic gene editing strategies utilize endogenous DNA repair pathways—nonhomologous end joining (NHEJ) or homology-directed repair (HDR)—to introduce targeted genomic modifications. Because HDR is restricted to dividing cells, whereas NHEJ functions in both dividing and non-dividing cells, NHEJ-based approaches are better suited for in vivo gene editing in the largely post-mitotic airway epithelium. Homology-independent targeted insertion (HITI), an NHEJ-based method, offers a promising strategy for cystic fibrosis (CF) gene therapy. Here, we applied HITI to drive the expression of a promoterless reporter through an exon trap strategy in both proliferating airway basal cells and well-differentiated primary airway epithelial cultures derived from transgenic ROSA^mTmG ferrets. We also established a versatile human gene editing reporter (GER) airway basal cell line capable of multipotent differentiation, enabling real-time visualization of editing outcomes and the quantitative assessment of HDR- and NHEJ-based editing efficiencies. Together, these platforms provide easily accessible tools for optimizing genome editing strategies in the respiratory epithelium and advancing clinically relevant delivery strategies for CF gene therapy. Full article

(This article belongs to the Special Issue Virology and Immunology of Gene Therapy 2025)

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12 pages, 682 KiB

Open AccessArticle

Neurological Manifestation of Canine Distemper Virus: Increased Risk in Young Shih Tzu and Lhasa Apso with Seasonal Prevalence in Autumn

by Heloisa L. Freire, Ítalo H. N. Iara, Luana S. R. Ribeiro, Paulo A. O. Gonçalves, David H. Matta and Bruno B. J. Torres

Viruses 2025, 17(6), 820; https://doi.org/10.3390/v17060820 - 6 Jun 2025

Abstract

Canine distemper virus (CDV) is a highly contagious disease with high morbidity and mortality rates in veterinary medicine. This retrospective study aimed to identify epidemiological characteristics and potential risk factors associated with CDV infection in dogs exhibiting neurological manifestations. The diagnosis was confirmed [...] Read more.

Canine distemper virus (CDV) is a highly contagious disease with high morbidity and mortality rates in veterinary medicine. This retrospective study aimed to identify epidemiological characteristics and potential risk factors associated with CDV infection in dogs exhibiting neurological manifestations. The diagnosis was confirmed through immunochromatographic antigen testing, RT-PCR, or Lentz corpuscles identification. Dogs diagnosed with central nervous system (CNS) disorders unrelated to CDV served as the control group. Age, breed, weight, sex, and neuter status were compared between groups using logistic regression (p < 0.05), the log-likelihood method, and log odds ratio (LOR) calculations. Clinical signs, seasonality, and vaccination protocols were documented. Prevalence, mortality, lethality, and survival rates were determined. Younger dogs (p = 0.00690; LOR = −0.01438) and Shih Tzu (p = 0.00007; LOR = 1.53774) and Lhasa Apso (p = 0.000264; LOR = 1.76084) showed a significantly increased likelihood of developing neurological signs due to CDV infection. Most CDV-infected dogs exhibited multifocal CNS involvement and accompanying extra-neural signs. The highest occurrence of CDV-related neurological signs was recorded in autumn. Many infected dogs had an updated vaccination protocol. The prevalence of dogs with CDV was 4.72%. Mortality and lethality rates were 1.94% and 47.06%, respectively. The median survival time was 754 days. The identified epidemiological characteristics and risk factors provide essential insights for improving preventive strategies against CDV infection. Full article

(This article belongs to the Special Issue Canine Distemper Virus)

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33 pages, 1491 KiB

Open AccessReview

The Evolving Role of Zika Virus Envelope Protein in Viral Entry and Pathogenesis

by Ashkan Roozitalab, Jiantao Zhang, Chenyu Zhang, Qiyi Tang and Richard Y. Zhao

Viruses 2025, 17(6), 817; https://doi.org/10.3390/v17060817 - 6 Jun 2025

Abstract

Zika virus (ZIKV) was first discovered in Uganda’s Zika Forest in 1947. The early African viruses posed little or no health risk to humans. Since then, ZIKV has undergone extensive genetic evolution and adapted to humans, and it now causes a range of [...] Read more.

Zika virus (ZIKV) was first discovered in Uganda’s Zika Forest in 1947. The early African viruses posed little or no health risk to humans. Since then, ZIKV has undergone extensive genetic evolution and adapted to humans, and it now causes a range of human diseases, including neurologically related diseases in adults and congenital malformations such as microcephaly in newborns. This raises a critical question as to why ZIKV has become pathogenic to humans, and what virological changes have taken place and enabled it to cause these diseases? This review aims to address these questions. Specifically, we focus on the ZIKV envelope (E) protein, which is essential for initiating infection and plays a crucial role in viral entry. We compare various virologic attributes of E protein between the ancestral African strains, which presumably did not cause human diseases, with epidemic strains responsible for current human pathogenesis. First, we review the role of the ZIKV E protein in viral entry and endocytosis during the viral life cycle. We will then examine how the E protein interacts with host immune responses and evades host antiviral responses. Additionally, we will analyze key differences in the sequence, structure, and post-translational modifications between African and Asian lineages, and discuss their potential impacts on viral infection and pathogenesis. Finally, we will evaluate neutralizing antibodies, small molecule inhibitors, and natural compounds that target the E protein. This will provide insights into the development of potential vaccines and antiviral therapies to prevent or treat ZIKV infections and associated diseases. Full article

(This article belongs to the Special Issue Preparation for the Next Potential Pandemic—Chikungunya, Dengue, Zika and Other Viruses)

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7 pages, 480 KiB

Open AccessConference Report

Navigating Virology’s Frontiers in Africa: Global Virus Network 2024 Durban Meeting

by Maggie L. Bartlett, Rubeshan Perumal, Sten H. Vermund and Salim Abdool Karim

Viruses 2025, 17(6), 819; https://doi.org/10.3390/v17060819 - 5 Jun 2025

Abstract

The Global Virus Network (GVN) is a voluntary consortium of virology laboratories and affiliated scientists that seek to prevent and control global viral threats. The meetings of the GVN are characterized by academic, health center, government, and industry participation, sharing information that is [...] Read more.

The Global Virus Network (GVN) is a voluntary consortium of virology laboratories and affiliated scientists that seek to prevent and control global viral threats. The meetings of the GVN are characterized by academic, health center, government, and industry participation, sharing information that is designed to further the mutual mission. In September 2024, the meeting in Durban, South Africa, highlighted diseases and investigators from Africa, and paid special attention to pandemic preparedness. Selected highlights from the meeting are presented here, along with a call-to-action in defense of global partnerships for research in the origins of human and animal viruses, the risk to humans from other animal sources, the pathogenesis of given viruses, and their prevention and treatment. Discussions of laboratory discovery science are juxtaposed with development of vaccines, antiviral drugs, immunotherapies, and innovative field strategies for control of viral diseases. Full article

(This article belongs to the Section General Virology)

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16 pages, 809 KiB

Open AccessArticle

DENV-2 Circulation and Host Preference Among Highly Anthropophilic, Outdoor-Biting Aedes aegypti in Dar es Salaam, Tanzania

by Frank S. C. Tenywa, Silvan Hälg, Haji Makame, Jason Moore, Osward Dogan, Harubu I. Mapipi, Jane J. Machange, Nasoro S. Lilolime, Lorenz M. Hofer, Lewis D. Batao, Tunu G. Mwamlima, Pie Müller and Sarah J. Moore

Viruses 2025, 17(6), 818; https://doi.org/10.3390/v17060818 - 5 Jun 2025

Abstract

In Tanzania, dengue outbreaks have occurred almost annually over the past decade, with each new outbreak becoming more severe. This study investigated the prevalence of dengue virus (DENV) serotypes in the wild Aedes aegypti and their blood sources to determine human exposure risk [...] Read more.

In Tanzania, dengue outbreaks have occurred almost annually over the past decade, with each new outbreak becoming more severe. This study investigated the prevalence of dengue virus (DENV) serotypes in the wild Aedes aegypti and their blood sources to determine human exposure risk in Dar es Salaam, Tanzania. A two-year longitudinal survey was conducted in the Ilala, Kinondoni, and Temeke districts of Dar es Salaam to sample Ae. aegypti mosquitoes using Biogents Sentinel trap (BGS), Prokopack aspiration, and Gravid Aedes trap (GAT). Collected mosquitoes were pooled in groups of 10 and tested for DENV1–4 serotypes using reverse transcription polymerase chain reaction (RT-qPCR). Blood meal sources were identified using an enzyme-linked immunosorbent assay (ELISA). Of 854 tested pools, only DENV-2 was detected and was found in all three districts: Temeke (3/371 pools), Ilala (1/206 pools), and Kinondoni (1/277 pools). Blood meal analysis showed a strong preference for humans (81%) as well as for mixed blood meals that contained human blood and other hosts (17%). Out of 354 collected hosts seeking Ae. aegypti, 78.5% were captured outdoors and 21.5% indoors. This study confirms the circulation of DENV-2 in Ae. aegypti populations, indicating a potential dengue outbreak risk in Tanzania. This study also demonstrates that xenomonitoring may be feasible in this setting. The mosquitoes’ strong preference for human hosts and predominance in outdoor settings pose challenges for dengue control efforts. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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20 pages, 5108 KiB

Open AccessArticle

Case Series of Adverse Pregnancy Outcomes Associated with Oropouche Virus Infection

by Daniele Barbosa de Almeida Medeiros, Juarez Antônio Simões Quaresma, Raimunda do Socorro da Silva Azevedo, Ana Cecilia Ribeiro Cruz, Sandro Patroca da Silva, Arnaldo Jorge Martins Filho, Bruno Tardelli Diniz Nunes, Lucas Rafael Santana Pinheiro, Jorge Rodrigues de Sousa, Jannifer Oliveira Chiang, Lívia Carício Martins, Consuelo Silva Oliveira, Ivy Tissuya Essashika Prazeres, Daniele Feitas Henriques, Camille Ferreira Oliveira, Valéria Lima Carvalho, Clarice Neuenschwander Lins Morais, Bartolomeu Acioli-Santos, Keilla Maria Paze Silva, Diego Arruda Falcão, Mayara Matias de Oliveira Marques Costa, Eduardo Augusto Duque Bezerra, Ana Márcia Drechsler Rio, Neijla Cristina Vieira Cardoso, Juliana Carla Serafim da Silva, Simone Gurmão Ramos, Erika Cavalcante Maranhão, José Lancart de Lima, Pedro Fernando da Costa Vasconcelos, Bruno Issao Matos Ishigami and Lívia Medeiros Neves Casseb Show full author list Hide full author list

Viruses 2025, 17(6), 816; https://doi.org/10.3390/v17060816 - 5 Jun 2025

Abstract

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. [...] Read more.

The Oropouche virus (OROV) is an arbovirus (Peribunyaviridae: Orthobunyavirus) that traditionally causes febrile outbreaks in Latin America’s Amazon region. Previously, OROV was not associated with severe pregnancy outcomes. During the 2022–2024 outbreak in Brazil, OROV expanded geographically, revealing links to adverse pregnancy outcomes. This study describes six cases with varied fetal outcomes, including miscarriage, antepartum, intrauterine fetal demise (IFD), and normal development, correlating with maternal symptoms but not symptom severity. Vertical transmission was confirmed by detecting OROV through RT-qPCR, ELISA, and immunohistochemistry in fetal tissues. Genome sequencing from an IFD case identified a novel reassortment pattern reported in the 2022–2024 outbreak. Severe encephalomalacia, meningoencephalitis, vascular compromise, and multi-organ damage were evident, underscoring the significant risk OROV poses to fetal development and emphasizing the need for further investigation. Full article

(This article belongs to the Special Issue Oropouche Virus (OROV): An Emerging Peribunyavirus (Bunyavirus))

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15 pages, 1894 KiB

Open AccessArticle

Spatiotemporal Distribution and Host–Vector Dynamics of Japanese Encephalitis Virus

by Qikai Yin, Bin Li, Ruichen Wang, Kai Nie, Shihong Fu, Songtao Xu, Fan Li, Qianqian Cui, Dan Liu, Huanyu Wang and Guodong Liang

Viruses 2025, 17(6), 815; https://doi.org/10.3390/v17060815 - 4 Jun 2025

Abstract

Japanese encephalitis (JE), a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV), remains a significant public health threat in Asia. Although vaccination programs have successfully reduced the incidence of JE, challenges persist in the adult population, and the emergence of rare [...] Read more.

Japanese encephalitis (JE), a mosquito-borne viral disease caused by the Japanese encephalitis virus (JEV), remains a significant public health threat in Asia. Although vaccination programs have successfully reduced the incidence of JE, challenges persist in the adult population, and the emergence of rare JEV genotypes poses additional risks. In this study, a phylogenetic analysis of the whole JEV genome sequence, along with a temporal–spatial analysis of isolates and a host–vector analysis, was used to examine the changes in JEV transmission dynamics before and after 2012. The results revealed persistent differences between the dominant G1 and G3 genotypes, as well as the re-emergence of G4 and G5 genotypes. Although JEV has been detected in non-traditional vectors and atypical mammalian hosts, Culex tritaeniorhynchus and pigs remain the primary vector and amplifying host, respectively. These findings underscore the need to enhance existing JEV genotype surveillance while addressing emerging threats from genotype diversity, host expansion, and geographic spread. Full article

(This article belongs to the Special Issue Mosquito-Borne Encephalitis Viruses)

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16 pages, 4257 KiB

Open AccessArticle

Discovery of Small-Molecule Inhibitors Against Norovirus 3CL^pro Using Structure-Based Virtual Screening and FlipGFP Assay

by Hao Shen, Shiqi Liu, Limin Shang, Yuchen Liu, Yijin Sha, Dingwei Lei, Yuehui Zhang, Chaozhi Jin, Shanshan Wu, Mingyang Zhang, Han Wen, Chenxi Jia and Jian Wang

Viruses 2025, 17(6), 814; https://doi.org/10.3390/v17060814 - 4 Jun 2025

Abstract

Norovirus, a major cause of acute gastroenteritis, possesses a single-stranded positive-sense RNA genome. The viral 3C-like cysteine protease (3CL^pro) plays a critical role in processing the viral polyprotein into mature non-structural proteins, a step essential for viral replication. Targeting 3CL^pro [...] Read more.

Norovirus, a major cause of acute gastroenteritis, possesses a single-stranded positive-sense RNA genome. The viral 3C-like cysteine protease (3CL^pro) plays a critical role in processing the viral polyprotein into mature non-structural proteins, a step essential for viral replication. Targeting 3CL^pro has emerged as a promising strategy for developing small-molecule inhibitors against Norovirus. In this study, we employed a combination of virtual screening and the FlipGFP assay to identify potential inhibitors targeting the 3CL^pro of Norovirus genotype GII.4. A library of approximately 58,800 compounds was screened using AutoDock Vina tool, yielding 20 candidate compounds based on their Max Affinity scores. These compounds were subsequently evaluated using a cell-based FlipGFP assay. Among them, eight compounds demonstrated significant inhibitory activity against 3CL^pro, with Gedatolisib showing the most potent effect (IC₅₀ = 0.06 ± 0.01 μM). Molecular docking and molecular dynamics simulations were conducted to explore the binding mechanisms and structural stability of the inhibitor–3CL^pro complexes. Our findings provide valuable insights into the development of antiviral drugs targeting Norovirus 3CL^pro, offering potential therapeutic strategies to combat Norovirus infections. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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11 pages, 487 KiB

Open AccessReview

Canine Distemper Virus in Mexico: A Risk Factor for Wildlife

by Juan Macías-González, Rebeca Granado-Gil, Lizbeth Mendoza-González, Cesar Pedroza-Roldán, Rogelio Alonso-Morales and Mauricio Realpe-Quintero

Viruses 2025, 17(6), 813; https://doi.org/10.3390/v17060813 - 3 Jun 2025

Abstract

Canine distemper is caused by a morbillivirus similar to others that affect livestock and humans. The increase in host range and its persistence in wildlife reservoirs complicate eradication considerably. Canine distemper virus has been reported in wildlife in Mexico since 2007. Dogs were [...] Read more.

Canine distemper is caused by a morbillivirus similar to others that affect livestock and humans. The increase in host range and its persistence in wildlife reservoirs complicate eradication considerably. Canine distemper virus has been reported in wildlife in Mexico since 2007. Dogs were previously considered the main reservoirs, but high vaccination coverage in the USA has helped control the disease, and racoons (Procyon lotor) are now recognized as the main reservoirs of the agent in the USA, since they live in high densities in urban environments (peridomestic), where contact with domestic and wildlife species is common. Racoons are now considered to spread CDV in wildlife species and zoo animals. Mexico is home to at least two wildlife species that have been reported as carriers of the CDV infection in studies in the USA. Raccoons and Coyotes are distributed in several Mexican states and could play the same reservoir role as for the US. In addition, the increase in non-traditional pets expands the availability of susceptible individuals to preserve CDV in domiciliary and peri-domiciliary environments, contributing to the spread of the disease. Combined with incomplete vaccination coverage in domestic canids, this could contribute to maintaining subclinical infections. Infected pets with incomplete vaccination schedules could also spread CDV to other canines or wildlife coexisting species. In controlled habitats, such as flora and fauna sanctuaries, protected habitats, zoo collections, etc., populations of wildlife species and stray dogs facilitate the spread of CDV infection, causing the spilling over of this infectious agent. Restricting domestic pets from wildlife habitats reduces the chance of spreading the infection. Regular epidemiological surveillance and specific wildlife conservation practices can contribute to managing threatened species susceptible to diseases like CDV. This may also facilitate timely interventions in companion animals which eventually minimize the impact of this disease in both scenarios. Aim: The review discusses the circulation of CDV in wildlife populations, and highlights the need for epidemiological surveillance in wildlife, particularly in endangered wildlife species from Mexico. Through an extensive review of recent scientific literature about CDV disease in wildlife that has been published in local and international databases, the findings were connected with the current needs of information from a local to global perspective, and conclusions were made to broaden the context of Mexican epidemiological scenarios as closely related to the neighboring regions. Full article

(This article belongs to the Section Animal Viruses)

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16 pages, 3770 KiB

Open AccessArticle

Novel Viral Sequences in a Patient with Cryptogenic Liver Cirrhosis Revealed by Serum Virome Sequencing

by Xiaoan Zhang, Ida X. Fan, Yanjuan Xu, Jody Rule, Long Ping Victor Tse, Mahmoud Reza Pourkarim, William M. Lee, Adrian M. Di Bisceglie and Xiaofeng Fan

Viruses 2025, 17(6), 812; https://doi.org/10.3390/v17060812 - 3 Jun 2025

Abstract

Clinical studies indicate the etiology of liver disease to be unknown in 5% to 30% of patients. A long-standing hypothesis is the existence of unknown viruses beyond hepatitis A through E virus. We conducted serum virome sequencing in nine patients with cryptogenic liver [...] Read more.

Clinical studies indicate the etiology of liver disease to be unknown in 5% to 30% of patients. A long-standing hypothesis is the existence of unknown viruses beyond hepatitis A through E virus. We conducted serum virome sequencing in nine patients with cryptogenic liver disease and identified eight contigs that could not be annotated. One was determined to be a contaminant, while two of seven contigs from an individual (Patient 3) were validated by reverse transcription and polymerase chain reaction (RT-PCR) and Sanger sequencing. The possibility of contamination was completely excluded through PCR, with templates extracted using different methods from samples taken at different time points. One of the contigs, Seq260, was characterized as negative-sense single-stranded DNA via enzymatic digestion and genome walking. Digital-droplet PCR revealed the copy number of Seq260 to be low: 343 copies/mL. Seq260-based nested PCR screening was negative in 200 blood donors and 225 patients with liver disease with/without known etiologies. None of the seven contigs from Patient 3 was mapped onto 118,713 viral metagenomic data. Conclusively, we discovered seven unknown contigs from a patient with cryptogenic liver cirrhosis. These sequences are likely from a novel human virus with a negative-sense, linear single-stranded DNA genome. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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12 pages, 1832 KiB

Open AccessArticle

Single-Cell Analysis of Host Responses in Bovine Milk Somatic Cells (bMSCs) Following HPAIV Bovine H5N1 Influenza Exposure

by Gagandeep Singh, Sujan Kafle, Patricia Assato, Mankanwal Goraya, Igor Morozov and Juergen A. Richt

Viruses 2025, 17(6), 811; https://doi.org/10.3390/v17060811 - 3 Jun 2025

Abstract

The 2024 outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in U.S. dairy cattle presented an unprecedented scenario where the virus infected bovine mammary glands and was detected in milk, raising serious concerns for public health and the dairy industry. Unlike previously [...] Read more.

The 2024 outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in U.S. dairy cattle presented an unprecedented scenario where the virus infected bovine mammary glands and was detected in milk, raising serious concerns for public health and the dairy industry. Unlike previously described subclinical influenza A virus (IAV) infections in cattle, H5N1 infection induced severe clinical symptoms, including respiratory distress, mastitis, and abnormal milk production. To understand the host immune responses and changes, particularly in the mammary gland, we performed single-cell RNA sequencing analysis on bovine milk somatic cells (bMSCs) in vitro exposed to an H5N1 isolate from an infected dairy farm. We identified ten distinct cell clusters and observed a shift toward type-2 immune responses, characterized by T cells expressing IL13 and GATA3, and three different subtypes of epithelial cells based on the expression of genes associated with milk production. Our study revealed temporal dynamics in cytokine expression, with a rapid decline in luminal epithelial cells and an increase in macrophages and dendritic cells, suggesting a role in increased antigen presentation. While viral RNA was detected in bulk-exposed bMSC samples via qRT-PCR, no viral reads were observed in the scRNA-seq data, indicating that the immune responses captured may be due to exposure to viral components rather than productive infection. This research fills a critical gap in understanding the immune responses of bovine mammary glands to H5N1 exposure and highlights the need for further investigation into therapeutic strategies for managing such outbreaks. Full article

(This article belongs to the Special Issue Advances in Endemic and Emerging Viral Diseases in Livestock)

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