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Volume 17
Issue 9
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Viruses, Volume 17, Issue 9 (September 2025) – 136 articles

Cover Story (view full-size image): Multipartite viruses achieve infection only through the precise interplay of their genome segments, a feature that has long challenged the development of experimental models. In this study, we report the construction of full-length tandem-dimer infectious clones for all eight genomic components of Milk Vetch Dwarf Virus (MDV). Agroinoculation of these clones successfully reconstituted systemic infections in Nicotiana benthamiana, Vicia faba, Vigna unguiculata and N. tabacum. Molecular assays confirmed the coordinated presence of viral segments, while host-dependent differences in their accumulation were revealed. This infectious clone system represents the first complete framework for MDV, providing a powerful platform to explore replication, host adaptation, and segment cooperation in nanoviruses. View this paper
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19 pages, 3052 KB  
Article
Genome-Wide Variation Profile of the Genus Tobamovirus
by Amany E. Gomaa and Hernan Garcia-Ruiz
Viruses 2025, 17(9), 1284; https://doi.org/10.3390/v17091284 - 22 Sep 2025
Viewed by 228
Abstract
The genus Tobamovirus belongs to the family Virgaviridae, and the genome consists of monopartite, positive, single-strand RNA. Most species contain four open reading frames encoding four essential proteins. Transmission occurs primarily through mechanical contact between plants, and in some cases, via seed [...] Read more.
The genus Tobamovirus belongs to the family Virgaviridae, and the genome consists of monopartite, positive, single-strand RNA. Most species contain four open reading frames encoding four essential proteins. Transmission occurs primarily through mechanical contact between plants, and in some cases, via seed dispersal. Tobamovirus fructirugosum (tomato brown rugose fruit virus, ToBRFV), the most recently described species in the genus, was first reported in 2015. It overcame genetic resistance that had been effective in tomato for sixty years, causing devastating losses in tomato production worldwide, and highlights the importance of understanding Tobamovirus genomic variation and evolution. In this study, we measured and characterized nucleotide variation for the entire genome and for all species in the genus Tobamovirus. Additionally, we measured the selection pressure acting on each open reading frame. Results showed that low nucleotide diversity and negative selection pressure are general features of tobamoviruses, with values that are approximately the same across open reading frames and without hypervariable areas. A comparison of nucleotide diversity between T. fructirugosum and its close relatives, T. tomatotessellati (tomato mosaic virus, ToMV) and T. tabaci (tobacco mosaic virus, TMV), showed low nucleotide diversity in the movement protein region harboring the resistance-breaking mutation. Furthermore, phylogenetic and diversity analyses showed that T. fructirugosum continues to evolve, and geographical distribution and host influence genomic diversity. Full article
(This article belongs to the Special Issue Plant Viral Pathogens: Innovations in Detection, Genetic Diversity, and Evolutionary Dynamics)
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10 pages, 683 KB  
Brief Report
Cervical Secretions from Women After Depot Medroxyprogesterone Acetate (Depo-Provera) Administration Promote HIV Infectivity Ex Vivo
by Carley Tasker, Natalie E. Roche, Yungtai Lo and Theresa L. Chang
Viruses 2025, 17(9), 1283; https://doi.org/10.3390/v17091283 - 22 Sep 2025
Viewed by 160
Abstract
Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. We have previously shown that Depo-Provera administration increases immune markers for HIV preference on peripheral and cervical CD4+ T cells but decreases the levels of most immune mediators [...] Read more.
Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. We have previously shown that Depo-Provera administration increases immune markers for HIV preference on peripheral and cervical CD4+ T cells but decreases the levels of most immune mediators at vaginal and cervical mucosa. In this study, we determined the effect of cervicovaginal secretions from women before (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment on HIV infectivity ex vivo. The effect of supernatants from vaginal, endocervical, and rectal swabs and from cervical cytobrush on HIV infectivity were assessed by a single-cycle infection assay using CCR5-using HIV-luciferase reporter viruses. We found that endocervical secretions from women after Depo-Provera treatment promoted HIV infectivity. When analyzing the association between endocervical mediator changes in response to Depo-Provera, available in our previous study, and the changes in HIV infectivity pre- and post-treatment, we found that changes in IL-17 and VEGF were positively associated with changes in HIV infectivity at visit 2 compared with visit 1, whereas changes in RANTES and IL-4 were negatively associated with HIV infectivity. The negative association between RANTES and HIV infectivity was also observed at visit 3 compared with visit 1. Additionally, changes in IL-1α at visit 3 were positively associated with changes in HIV infectivity compared with visit 1. These findings suggest that Depo-Provera may increase the HIV risk by shifting the mucosal milieu that promotes HIV infectivity. Full article
(This article belongs to the Special Issue Viruses in the Reproductive Tract)
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17 pages, 2829 KB  
Article
The ORF1ab of Feline Coronavirus Plays a Critical Role in Regulating the Innate Immune Response
by Haorong Gu, Chuqiao Xia, Hongtao Kang and Honglin Jia
Viruses 2025, 17(9), 1282; https://doi.org/10.3390/v17091282 - 22 Sep 2025
Viewed by 189
Abstract
Feline coronaviruses (FCoVs) are divided into two groups: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV is responsible for the severe disease known as feline infectious peritonitis, while FECV typically causes mild symptoms, such as diarrhea, and often does not [...] Read more.
Feline coronaviruses (FCoVs) are divided into two groups: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV is responsible for the severe disease known as feline infectious peritonitis, while FECV typically causes mild symptoms, such as diarrhea, and often does not lead to any disease at all. Currently, it is not possible to distinguish between FIPV and FECV at the molecular level. Therefore, there is an urgent need to understand the molecular features of FIPV. Here, we generated a recombinant virus by replacing the ORF1ab region and the coding sequence for the spike (S) protein of an FECV with the corresponding sequences from FIPVs. The recombinant virus (recFECV-SDF-2-1abFIPV) exhibited similar growth kinetics to its parental strain. Our analysis revealed that the replacement of the ORF1ab in the FECV caused significant alterations in protein expression within the host cells. Furthermore, the presence of the ORF1ab from the FIPV strain resulted in enhanced suppression of the innate immune response compared to the parental strain, as determined through proteomic and transcriptomic studies. Additionally, we demonstrated that the papain-like protease 2 (PL2pro) of the non-structural protein 3 (NSP3) from both FIPV and FECV functions in immune suppression, and the protease activity is required for this function. Full article
(This article belongs to the Section Animal Viruses)
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1 pages, 163 KB  
Correction
Correction: Galuzo et al. CLEC5A Activation in Inflammatory Monocytes: A Mechanism for Enhanced Adaptive Immunity Following COVID-19 mRNA Vaccination in a Preclinical Study. Viruses 2025, 17, 1233
by Renan Galuzo, Thiago Lazari Machado, Ryann de Souza Nascimento, Jorvan Ramos de Medeiros, Luciana Neves Tubarão, Jane Silva, Vanessa Pimenta Rocha, Tamiris Azamor, Felipe Soares Coelho, Andrea Marques Vieira da Silva, Lorenna Carvalho da Rosa, Juliana Fernandes Amorim da Silva, Renata Tourinho Santos, Rodrigo Müller, Carolina Baeta Salvador Várady, Ana Paula Dinis Ano Bom, Patricia Cristina da Costa Neves and Juliana Gil Melgaço
Viruses 2025, 17(9), 1281; https://doi.org/10.3390/v17091281 - 22 Sep 2025
Viewed by 99
Abstract
In the original publication [...] Full article
16 pages, 2566 KB  
Article
Ruvidar®—An Effective Anti-Herpes Simplex Virus Agent
by Kevin M. Coombs, Roger DuMoulin-White and Arkady Mandel
Viruses 2025, 17(9), 1280; https://doi.org/10.3390/v17091280 - 20 Sep 2025
Viewed by 429
Abstract
Infectious agents account for millions of deaths every year. The Herpes Simplex Viruses (HSVs) are large double-stranded DNA viruses that infect more than 90% of the human population and can establish life-long latency in human hosts. Currently, effective FDA approved anti-herpetic drugs include [...] Read more.
Infectious agents account for millions of deaths every year. The Herpes Simplex Viruses (HSVs) are large double-stranded DNA viruses that infect more than 90% of the human population and can establish life-long latency in human hosts. Currently, effective FDA approved anti-herpetic drugs include acyclovir and later-generation derivatives (valacyclovir and famciclovir), which inhibit viral DNA synthesis. In previous work, we demonstrated that the small molecule Ruvidar® could inhibit numerous pathogenic human viruses when added to solutions of viruses both with and without light activation. In these experiments, we evaluated the ability of Ruvidar® to restrict HSV-1 replication in Vero cells, both by itself and in combination with acyclovir and metformin in the absence of light activation to mimic deep tissue. Ruvidar® successfully inhibited HSV-1 replication at significantly lower concentrations and more effectively than either acyclovir or metformin alone. We also discovered additive and synergistic anti-HSV-1 effects when combinational therapy was tested. Ruvidar® also restricted HSV-1 replication in human U251 glioblastoma astrocytoma cells, remained highly effective against acyclovir-resistant HSV-1 mutants, and protected infected cells from virus-induced cytopathology. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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17 pages, 1606 KB  
Article
Structural Insights into the Nuclear Import of Haliotid Herpesvirus 1 Large Tegument Protein Homologue
by Babu Kanti Nath, Crystall M. D. Swarbrick, Renate H. M. Schwab, Daryl Ariawan, Ole Tietz, Jade K. Forwood and Subir Sarker
Viruses 2025, 17(9), 1279; https://doi.org/10.3390/v17091279 - 20 Sep 2025
Viewed by 187
Abstract
Abalone are highly susceptible to haliotid herpesvirus 1 (HaHV1), the causative agent of abalone viral ganglioneuritis (AVG), a re-emerging disease responsible for significant mortality events in both wild and farmed populations. Currently, there are no effective antiviral treatments or preventive measures available against [...] Read more.
Abalone are highly susceptible to haliotid herpesvirus 1 (HaHV1), the causative agent of abalone viral ganglioneuritis (AVG), a re-emerging disease responsible for significant mortality events in both wild and farmed populations. Currently, there are no effective antiviral treatments or preventive measures available against HaHV1, which is partly due to the limited understanding of the immune responses and viral pathogenesis in this non-model marine invertebrate. This highlights the urgent need for novel intervention strategies, including investigations into the molecular mechanisms underlying HaHV1 infection. In other herpesviruses, the large tegument protein UL36 plays a crucial role in transporting the viral capsid to the host cell’s nuclear pore complex (NPC), mediated by N-terminal nuclear localization signals (NLSs). However, the nuclear import mechanism of UL36 homologue (UL36h) in HaHV1 remains largely uncharacterized. In this study, we identified and functionally characterized the NLS motif within HaHV1 UL36h and elucidated its interactions with the importin alpha (IMPα) nuclear import receptor. Through a combination of high-resolution crystallography and quantitative binding assays, we determined the key residues responsible for binding to IMPα and demonstrated isoform-specific variations in binding affinity. Our biochemical and structural analyses confirmed key interactions within the NLS that are essential for IMPα interactions. These findings advance our molecular understanding of HaHV1 host interactions and pave the way for the development of targeted antiviral strategies against abalone herpesvirus infection. Full article
(This article belongs to the Special Issue Veterinary Virology: Unraveling Host–Pathogen Interactions for Animal Health)
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15 pages, 1561 KB  
Article
RNA Polymerase III Regulates HIV Replication and Latency
by Landon Thompson, Imran Jamal, Juthika Das, Casey Dang, Zhenzi Hong, Doran Katz, Alberto Bosque and Vir B. Singh
Viruses 2025, 17(9), 1278; https://doi.org/10.3390/v17091278 - 20 Sep 2025
Viewed by 277
Abstract
The elimination of HIV latent reservoirs is an extremely challenging task due to the interplay of multiple mechanisms regulating latency. Thus, we need to identify novel strategies to target heterogeneous reservoirs uniformly. Recent reports have provided intriguing evidence for the novel antiviral function [...] Read more.
The elimination of HIV latent reservoirs is an extremely challenging task due to the interplay of multiple mechanisms regulating latency. Thus, we need to identify novel strategies to target heterogeneous reservoirs uniformly. Recent reports have provided intriguing evidence for the novel antiviral function of RNA Polymerase III (RNAP III), which remains to be further explored. In this study, we evaluated the role of RNA Pol III in regulating HIV latency and replication. We first demonstrated that the pharmacological inhibition of RNAP III can lead to a strong reactivation of latency in cell lines representing both T and monocytic cellular reservoirs. Next, we investigated the involvement of RNA Pol III in regulating HIV-1 replication using HIV-1 pseudotyped (DuoFluo) virus and HIV-1-Bal in THP-1 and Sup-T1 cells. We show that the pharmacological inhibition of RNAP III significantly induced HIV transcription. These findings were further confirmed in physiologically relevant primary CD4 T cells, and a consistent increase in HIV transcription was observed up to 72 h. Collectively, our study suggests that inhibition of RNAP III can increase the rate of HIV transcription, while the total HIV DNA remains unchanged. Overall, our study identifies a previously unknown role of RNA Pol III in restricting HIV transcription and advocates that targeting RNAP III-driven mechanisms could be a novel strategy to reactivate HIV latent reservoirs. Full article
(This article belongs to the Special Issue Cellular Mechanisms Regulating HIV Replication, 2nd Edition)
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29 pages, 7171 KB  
Article
Antibody-Dependent Enhancement of Porcine Reproductive and Respiratory Syndrome Virus Infection Antagonizes the Secretion of Type I Interferons in Porcine Alveolar Macrophages by Interfering with the Retinoic Acid-Inducible Gene I/Melanoma Differentiation-Associated Gene 5 Pathway via Fc Gamma Receptor I
by Liujun Zhang, Aiyang Wang, Weizhen Chen, Xing Feng, Bo Wang, Shaojun He and Hongjie Fan
Viruses 2025, 17(9), 1277; https://doi.org/10.3390/v17091277 - 20 Sep 2025
Viewed by 213
Abstract
Type I interferons (IFNs), mainly IFN-α and IFN-β, play an essential role in defending against viral invasion by inducing the host’s innate antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is known to impair the IFN responses of infected hosts through the [...] Read more.
Type I interferons (IFNs), mainly IFN-α and IFN-β, play an essential role in defending against viral invasion by inducing the host’s innate antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is known to impair the IFN responses of infected hosts through the antibody-dependent enhancement (ADE) infection pathway, but the precise mechanisms employed are poorly understood. In this study, we showed that PRRSV alone induced a strong secretion of IFN-α and IFN-β in infected porcine alveolar macrophages (PAMs) by activating the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) signaling pathway. By contrast, ADE infection of PRRSV significantly down-regulated the production levels of IFN-α and IFN-β in PAMs by negatively regulating the RIG-I/MDA5 signaling pathway and considerably enhancing the replication level of PRRSV in PAMs. Next, small interfering RNA (siRNA) experiments revealed that Fc gamma receptor I (FcγRI) was responsible for the ADE infection of PRRSV in PAMs. In addition, we observed that FcγRI mediated the potent inhibition of IFN-α and IFN-β production through blocking the activation of the RIG-I/MDA5 signaling pathway in PAMs. Further, we found that FcγRI effectively inhibited PRRSV-induced synthesis of IFN-α and IFN-β by negatively regulating PRRSV-induced activation of the RIG-I/MDA5 signaling pathway in PAMs and significantly increased the viral production of PRRSV in PAMs. In conclusion, these results suggest that ADE infection of PRRSV may antagonize the secretion of type I IFNs (IFN-α/β) by interfering with the RIG-I/MDA5 pathway via FcγRI in PAMs, thereby facilitating the proliferation level of PRRSV in PAMs. Full article
(This article belongs to the Section Animal Viruses)
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28 pages, 3125 KB  
Review
Molecular Insights into HPV-Driven Head and Neck Cancers: From Viral Oncoproteins to Precision Therapeutics
by Mustafa Ozdogan, Gizem Tutkun, Muharrem Okan Cakir and Gholam Hossein Ashrafi
Viruses 2025, 17(9), 1276; https://doi.org/10.3390/v17091276 - 20 Sep 2025
Viewed by 553
Abstract
Human papillomavirus (HPV) plays a major role in the development of head and neck cancers (HNCs), particularly oropharyngeal squamous cell carcinoma. This review highlights the key molecular mechanisms of HPV-driven carcinogenesis, focusing on the oncogenic E6 and E7 proteins and their disruption of [...] Read more.
Human papillomavirus (HPV) plays a major role in the development of head and neck cancers (HNCs), particularly oropharyngeal squamous cell carcinoma. This review highlights the key molecular mechanisms of HPV-driven carcinogenesis, focusing on the oncogenic E6 and E7 proteins and their disruption of tumor suppressor pathways and epigenetic regulation. We discuss the rising prevalence of HPV-related HNCs, their distinct clinical features, and diagnostic approaches such as p16 immunohistochemistry and HPV DNA/RNA detection. HPV-positive tumors show better prognosis and response to treatment, prompting interest in therapy de-escalation. Emerging strategies including immune checkpoint inhibitors, therapeutic vaccines, CRISPR-based gene editing, and ctDNA monitoring are advancing precision oncology in this field. We also examine the preventive potential of HPV vaccination and ongoing research into its role across various HNC subtypes. A deeper understanding of HPV’s molecular impact may guide more effective, targeted, and less toxic interventions. Full article
(This article belongs to the Special Issue Oncogenic Infections and Cancer: Clinical Insights and Emerging Therapeutics)
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25 pages, 1719 KB  
Article
Living Together Apart: Quantitative Perspectives on the Costs and Benefits of a Multipartite Genome Organization in Viruses
by Marcelle L. Johnson, Dieke Boezen, Alexey A. Grum-Grzhimaylo, René A. A. van der Vlugt, J. Arjan G. M. de Visser and Mark P. Zwart
Viruses 2025, 17(9), 1275; https://doi.org/10.3390/v17091275 - 20 Sep 2025
Viewed by 133
Abstract
Background: Multipartite viruses individually package their multiple genome segments into virus particles, necessitating the transmission of multiple virus particles for effective viral spread. This dependence poses a cost in the form of reduced transmission compared to monopartite viruses, which only have a single [...] Read more.
Background: Multipartite viruses individually package their multiple genome segments into virus particles, necessitating the transmission of multiple virus particles for effective viral spread. This dependence poses a cost in the form of reduced transmission compared to monopartite viruses, which only have a single genome segment. The notable cost of a multipartite genome organization has spurred debate on why multipartite viruses are so common among plant viruses, including a search for benefits associated with this organizational form. Methods: We investigated the costs and benefits of multipartite viruses with three approaches. First, we reanalyzed dose–response data to measure the cost of multipartition to between-host transmission for multipartite viruses. Second, we developed a simulation model to explore when the sharing of viral gene products between cells is beneficial. Third, we tested whether multipartite viruses have a broad host range by estimating the host range for plant viruses using metagenomics data. Results: We find that the observed cost to transmission exceeds theoretical predictions. We predict that a virus gene-product-sharing strategy only confers benefits under limited conditions, suggesting that this strategy may not be common. Our results suggest that multipartite and segmented viruses have broader host ranges than monopartite viruses. Conclusions: Our analyses also suggest there is limited evidence for the costs and benefits of a multipartite organization, and we argue that the diversity of multipartite virus–host systems demands pluralistic explanatory frameworks. Full article
(This article belongs to the Section General Virology)
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16 pages, 2156 KB  
Article
Comparative Acquisition, Transmission, and Retention of Distinct Grapevine Red Blotch Virus Isolates in Relation to the Genotype and Sex of Spissistilus festinus, the Treehopper Vector
by Victoria J. Hoyle, Anna O. Wunsch, Heather McLane, Scottie Browning, Madison T. Flasco, Elizabeth J. Cieniewicz and Marc Fuchs
Viruses 2025, 17(9), 1274; https://doi.org/10.3390/v17091274 - 20 Sep 2025
Viewed by 224
Abstract
Grapevine red blotch virus (GRBV), the causal agent of red blotch disease of grapevines, is transmitted by Spissistilus festinus, the threecornered alfalfa hopper. Isolates of GRBV belong to two phylogenetic clades (I and II) and S. festinus is a dimorphic insect, with [...] Read more.
Grapevine red blotch virus (GRBV), the causal agent of red blotch disease of grapevines, is transmitted by Spissistilus festinus, the threecornered alfalfa hopper. Isolates of GRBV belong to two phylogenetic clades (I and II) and S. festinus is a dimorphic insect, with two genotypes found in the western (California, CA) and the southeastern (SE) regions of the United States. The transmission of GRBV by S. festinus is circulative and nonpropagative, yet some parameters of transmission remain to be characterized. Here, we compared the acquisition, transmission, and retention of GRBV isolates from phylogenetic clades I and II by S. festinus males and females of the two genotypes. Results indicated that the SE genotype acquired GRBV more efficiently (72.5%, 29/40) than the CA genotype (22.5%, 18/80), with differences in acquisition observed between males (32.5%, 26/80) and females (52.5%, 21/40) of the two S. festinus genotypes and between GRBV isolates of phylogenetic clades I (29%, 23/80) and II (60%, 24/40). Following acquisition, both S. festinus genotypes and sexes retained GRBV isolates of phylogenetic clades I and II for at least 60 days without access to an infected plant. For transmission, the GRBV isolate of phylogenetic clade II was more efficiently transmitted by the SE genotype (54%, 13/24) than the CA genotype (17%, 4/24) and SE females (75%, 12/16) were significantly more efficient transmitters of GRBV than CA females (19%, 3/16). Together, our findings revealed that S. festinus genotype, sex, and virus isolate influence GRBV acquisition and transmission but not retention. This research addressed important knowledge gaps in S. festinus-mediated transmission of GRBV that are essential for advancing red blotch disease epidemiology and developing appropriate disease management responses. Full article
(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)
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16 pages, 2323 KB  
Article
Discovery of Landscape Phage Probes Against Cellular Communication Network Factor 1 (CCN1/Cyr61)
by James W. Gillespie and Valery A. Petrenko
Viruses 2025, 17(9), 1273; https://doi.org/10.3390/v17091273 - 19 Sep 2025
Viewed by 202
Abstract
Detection of cancer biomarkers at the earliest stages of disease progression is commonly assumed to extend the overall quality of life for cancer patients as the result of earlier clinical management of the disease. Therefore, there is an urgent need for the development [...] Read more.
Detection of cancer biomarkers at the earliest stages of disease progression is commonly assumed to extend the overall quality of life for cancer patients as the result of earlier clinical management of the disease. Therefore, there is an urgent need for the development of standardized, sensitive, robust, and commonly available screening and diagnostic tools for detecting the earliest signals of neoplastic pathology progression. Recently, a new paradigm of cancer control, known as multi-cancer detection (MCD), evolved, which measures the composition of cancer-related molecular analytes in the patient’s fluids using minimally invasive techniques. In this respect, the “Holy Grail” of cancer researchers and bioengineers for decades has been composing a repertoire or molecular sensing probes that would allow for the diagnosis, prognosis, and monitoring of cancer diseases via their interaction with cell-secreted and cell-associated cancer antigens and biomarkers. Therefore, the current trend in screening and detection of cancer-related pathologies is the development of portable biosensors for mobile laboratories and individual use. Phage display, since its conception by George Smith 40 years ago, has emerged as a premier tool for molecular evolution in molecular biology with widespread applications including identification and screening of cancer biomarkers, such as Circulating Cellular Communication Network Factor 1 (CCN1), an extracellular matrix-associated signaling protein responsible for a variety of cellular functions and has been shown to be overexpressed as part of the response to various pathologies including cancer. We hypothesize that CCN1 protein can be used as a soluble marker for the early detection of breast cancer in a multi-cancer detection (MCD) platform. However, validated probes have not been identified to date. Here, we screened the multi-billion clone landscape phage display library for phages interacting specifically with immobilized CCN1 protein. Through our study, we discovered a panel of 26 different phage-fused peptides interacting selectively with CCN1 protein that can serve for development of a novel phage-based diagnostic platform to monitor changes in CCN1 serum concentration by liquid biopsy. Full article
(This article belongs to the Special Issue Phage Display in Cancer Diagnosis and Screening)
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22 pages, 3096 KB  
Article
Deep Learning-Based Automatic Segmentation and Analysis of Mitochondrial Damage by Zika Virus and SARS-CoV-2
by Brianda Alexia Agundis-Tinajero, Miguel Ángel Coronado-Ipiña, Ignacio Lara-Hernández, Rodrigo Aparicio-Antonio, Anita Aguirre-Barbosa, Gisela Barrera-Badillo, Nidia Aréchiga-Ceballos, Irma López-Martínez, Claudia G Castillo, Vanessa Labrada-Martagón, Mauricio Comas-García and Aldo Rodrigo Mejía-Rodríguez
Viruses 2025, 17(9), 1272; https://doi.org/10.3390/v17091272 - 19 Sep 2025
Viewed by 479
Abstract
Viruses can induce various mitochondrial morphological changes, which are associated with the type of immune response. Therefore, characterization and analysis of mitochondrial ultrastructural changes could provide insights into the kind of immune response elicited, especially when compared to uninfected cells. However, this analysis [...] Read more.
Viruses can induce various mitochondrial morphological changes, which are associated with the type of immune response. Therefore, characterization and analysis of mitochondrial ultrastructural changes could provide insights into the kind of immune response elicited, especially when compared to uninfected cells. However, this analysis is highly time-consuming and susceptible to observer bias. This work presents the development of a deep learning-based approach for the automatic identification, segmentation, and analysis of mitochondria from thin-section transmission electron microscopy images of cells infected with two SARS-CoV-2 variants or the Zika virus, utilizing a convolutional neural network with a U-Net architecture. A comparison between manual and automatic segmentations, along with morphological metrics, was performed, yielding an accuracy greater than 85% with no statistically significant differences between the manual and automatic metrics. This approach significantly reduces processing time and enables a prediction of the immune response to viral infections by allowing the detection of both intact and damaged mitochondria. Therefore, the proposed deep learning-based tool may represent a significant advancement in the study and understanding of cellular responses to emerging pathogens. Additionally, its applicability could be extended to the analysis of other organelles, thereby opening up new opportunities for automated studies in cell biology. Full article
(This article belongs to the Section Animal Viruses)
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20 pages, 729 KB  
Article
Linking Pollution and Viral Risk: Detection of Dioxins and Coronaviruses in Cats and Dogs
by Francesco Serra, Silvia Canzanella, Sergio Brandi, Gerardo Picazio, Anna Maria Pugliese, Luca Del Sorbo, Gianluca Miletti, Enza Ragosta, Emanuela Sannino, Filomena Fiorito, Mauro Esposito, Esterina De Carlo, Giovanna Fusco and Maria Grazia Amoroso
Viruses 2025, 17(9), 1271; https://doi.org/10.3390/v17091271 - 19 Sep 2025
Viewed by 177
Abstract
Viral and chemical analyses were performed on 80 dead cats and 51 dead dogs from the Campania Region (Southern Italy), with the aim of evaluating in vivo the potential correlation between coronavirus (CoV) infections and levels of environmental pollutants such as dioxins and [...] Read more.
Viral and chemical analyses were performed on 80 dead cats and 51 dead dogs from the Campania Region (Southern Italy), with the aim of evaluating in vivo the potential correlation between coronavirus (CoV) infections and levels of environmental pollutants such as dioxins and PCSs (PCDD/F, DL-PCB and NDL-PCB). The overall viral prevalence was 16.3% in cats and 23.5% in dogs. Both feline coronavirus (FCoV) and canine coronavirus (CCoV) were identified, with variable detection rates in all the other organs investigated, supporting studies that provide evidence of systemic viral spread. The highest prevalence of coronaviruses (CoVs) was observed in Naples (19.2% for FCoV; 30.7% for CCoV) and Caserta (11.1% for FCoV; 50.0% for CCoV), areas that include municipalities with the highest Municipality Index of Environmental Pressure (MIEP) scores. Chemical analyses showed that DL-PCBs were present at more elevated concentrations in CoV-infected dogs and cats than in non-infected animals, whereas ∑NDL-PCB and ∑PCDD/F were detected in greater amounts in non-infected subjects. Among PCDDs, the congener 2,3,7,8-TCDD displayed different distribution patterns between infected and non-infected animals. In cats, 70.0% of FCoV-positive individuals had 2,3,7,8-TCDD levels above the limit of quantification (LOQ), compared with 38.0% of FCoV-negative cats. In dogs, 78.0% of CCoV-infected animals exceeded the LOQ, compared with 20.0% of non-infected ones; this difference was statistically significant. The results of the study suggest that elevated levels of 2,3,7,8-TCDD may be associated with CCoV infection and replication in dogs, suggesting a possible relationship between environmental pollution and susceptibility to coronavirus infections. Full article
(This article belongs to the Section Animal Viruses)
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14 pages, 3913 KB  
Article
Isolation of Porcine Adenovirus Serotype 5 and Construction of Recombinant Virus as a Vector Platform for Vaccine Development
by Qianhua He, Jun Wu, Zhilong Bian, Yuan Sun and Jingyun Ma
Viruses 2025, 17(9), 1270; https://doi.org/10.3390/v17091270 - 19 Sep 2025
Viewed by 207
Abstract
Porcine adenovirus serotype 5 (PAdV-5) is an emerging viral vector platform for veterinary vaccines; however, its genomic plasticity and essential replication elements remain incompletely characterized. This study reports the isolation and reverse genetic manipulation of a novel PAdV-5 strain (GD84) from diarrheic piglets [...] Read more.
Porcine adenovirus serotype 5 (PAdV-5) is an emerging viral vector platform for veterinary vaccines; however, its genomic plasticity and essential replication elements remain incompletely characterized. This study reports the isolation and reverse genetic manipulation of a novel PAdV-5 strain (GD84) from diarrheic piglets in China. PCR screening of 167 clinical samples revealed a PAdV-5 detection rate of 38.3% (64/167), with successful isolation on ST cells after three blind passages. The complete GD84 genome is 32,620 bp in length and exhibited 99.0% nucleotide identity to the contemporary strain Ino5, but only 97.0% to the prototype HNF-70. It features an atypical GC content of 51.0% and divergent structural genes—most notably the hexon gene (89% identity to HNF-70)—suggesting altered immunogenicity. Using Red/ET recombineering, we established a rapid (less than 3 weeks) reverse genetics platform and generated four E3-modified recombinants: ΔE3-All-eGFP, ΔE3-12.5K-eGFP, ΔE3-12.5K+ORF4-eGFP, and E3-Insert-eGFP. Crucially, the ΔE3-All-eGFP construct (complete E3 deletion) failed to be rescued, while constructs preserving the 12.5K open reading frame (ORF) yielded replication-competent viruses with sustained eGFP expression over three serial passages and titers over 107.0 TCID50/mL. Fluorescence intensity was inversely correlated with genome size, as the full-length E3-Insert-eGFP virus showed reduced expression compared with the ΔE3 variants. Our work identifies the 12.5K ORF as essential for PAdV-5 replication and provides an optimized vaccine engineering platform that balances genomic payload capacity with replicative fitness. Full article
(This article belongs to the Section Animal Viruses)
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12 pages, 725 KB  
Review
Insect-Specific Viruses and Their Emerging Role in Plant Disease Mitigation
by Jianing Lei, Jingna Yuan, Mengnan Chen and Qianzhuo Mao
Viruses 2025, 17(9), 1269; https://doi.org/10.3390/v17091269 - 19 Sep 2025
Viewed by 285
Abstract
Insect vectors play a pivotal role in the emergence and dissemination of plant viral diseases. Beyond their function in transmitting plant viruses, these insects harbor diverse insect-specific viruses (ISVs). Advances in high-throughput sequencing (HTS) have uncovered virus diversity and prevalence in insects that [...] Read more.
Insect vectors play a pivotal role in the emergence and dissemination of plant viral diseases. Beyond their function in transmitting plant viruses, these insects harbor diverse insect-specific viruses (ISVs). Advances in high-throughput sequencing (HTS) have uncovered virus diversity and prevalence in insects that far exceed previous estimations. However, current knowledge of ISVs remains predominantly limited to genomic sequencing information. Investigating the fundamental biology of ISVs, their effects on insect physiology, and their modulation of vector competence is critical for deciphering complex virus–virus and virus–insect interactions. Such research holds substantial promise for developing innovative biocontrol strategies against plant viral pathogens. This review synthesizes current insights into the interplay between plant viruses and their insect vectors, explores the discovery and functional roles of ISVs, and discusses the potential application of ISVs in mitigating plant viral diseases. Understanding these dynamic relationships offers new avenues for sustainable plant disease management. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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14 pages, 751 KB  
Review
Tomato Bushy Stunt Virus (TBSV): From a Plant Pathogen to a Multifunctional Biotechnology Platform
by Almas Madirov, Nurgul Iksat and Zhaksylyk Masalimov
Viruses 2025, 17(9), 1268; https://doi.org/10.3390/v17091268 - 19 Sep 2025
Viewed by 260
Abstract
Plant viruses have evolved from being viewed exclusively as pathogens into versatile and powerful tools for modern biotechnology. Among them, Tomato bushy stunt virus (TBSV) holds a special place due to its well-studied molecular biology and unique structural properties. This review systematizes the [...] Read more.
Plant viruses have evolved from being viewed exclusively as pathogens into versatile and powerful tools for modern biotechnology. Among them, Tomato bushy stunt virus (TBSV) holds a special place due to its well-studied molecular biology and unique structural properties. This review systematizes the knowledge on TBSV’s dual role as a multifunctional platform. On one hand, we cover its application as a viral vector for the highly efficient expression of recombinant proteins in plants, as well as a tool for functional genomics, including Virus-Induced Gene Silencing (VIGS) and the delivery of CRISPR/Cas9 gene-editing components. On the other hand, we provide a detailed analysis of the use of the stable and monodisperse TBSV virion in nanobiotechnology. Its capsid serves as an ideal scaffold for creating next-generation vaccine candidates, platforms for targeted drug delivery to tumor cells, and as a building block for the programmable self-assembly of complex nanoarchitectures. In conclusion, key challenges limiting the widespread adoption of the platform are discussed, including the genetic instability of vectors and difficulties in scalable purification, along with promising strategies to overcome them. Full article
(This article belongs to the Special Issue Application of Plant Viruses in Biotechnology)
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13 pages, 1969 KB  
Article
Probing Viral Dark Matter: Comparative Genomics of Atypical Bacillus Phage YungSlug
by Allison A. Johnson, Andrew Hale, Amine Sehnouni, Zainab Gbadamosi and Bret M. Boyd
Viruses 2025, 17(9), 1267; https://doi.org/10.3390/v17091267 - 19 Sep 2025
Viewed by 237
Abstract
Bacillus phage YungSlug is a novel phage with a genome that has limited homology to known viruses. To better understand this unique phage, we searched for close relatives of YungSlug using traditional comparative genomics approaches and a broad search of a large protein [...] Read more.
Bacillus phage YungSlug is a novel phage with a genome that has limited homology to known viruses. To better understand this unique phage, we searched for close relatives of YungSlug using traditional comparative genomics approaches and a broad search of a large protein database. YungSlug shares only 9% genome alignment with Bacillus phage Nachito, its closest relative, and less than 1% with others in its subfamily. A search for homologs in the NCBI nr database was dominated by low percent identity homologs from viral, bacteria, and environmental sources, returning matches for only 50% of the predicted proteins in YungSlug’s genome. Additionally, a set of 21 conserved proteins was identified that may define a core gene set for the Spounavirinae subfamily of Herelleviridae. These findings highlight the diversity of phages infecting Bacillus and highlight gaps in our knowledge of the Bacillus-infecting phage community. Full article
(This article belongs to the Special Issue Bacteriophage Diversity, 2nd Edition)
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13 pages, 709 KB  
Article
Co-Detection of ADV, Influenza B, and HPIV: Independent Risk Factors for SMPP with Changes in NPIs
by Linlin Huang and Ting Shi
Viruses 2025, 17(9), 1266; https://doi.org/10.3390/v17091266 - 19 Sep 2025
Viewed by 247
Abstract
Background: This study investigated the epidemiology of Mycoplasma pneumoniae (MP) in children with acute respiratory tract infections (ARTIs) and explored the risk factors for severe mycoplasma pneumoniae pneumonia (SMPP) in children. Methods: A retrospective analysis was conducted on 36,380 children with acute respiratory [...] Read more.
Background: This study investigated the epidemiology of Mycoplasma pneumoniae (MP) in children with acute respiratory tract infections (ARTIs) and explored the risk factors for severe mycoplasma pneumoniae pneumonia (SMPP) in children. Methods: A retrospective analysis was conducted on 36,380 children with acute respiratory infections who underwent multiplex real-time polymerase chain reaction (RT-PCR) assays for nine respiratory pathogens from September 2021 to November 2024. Results: A total of 36,380 children with ARTIs were enrolled in this study. The co-detection rate of MP with other pathogens was significantly higher in the post-NPIs period than in the NPIs period (36.5% vs. 25.7%, p < 0.01). Multivariate regression identified the detection of influenza A virus (InfA), InfB, human parainfluenza virus (HPIV), human bocaparvovirus (HBoV), human rhinovirus (HRV), adenovirus (ADV), human respiratory syncytial virus (HRSV), and human metapneumovirus (HMPV) as protective factors against MP epidemics (p < 0.01); meanwhile, older age, the cancellation of NPIs, and summer–autumn seasons were found to be risk factors. After adjusting for sex, age, period, season, and pathogens, InfB (OR: 3.009, 95%CI: 1.041–8.697, p = 0.042), HPIV (OR: 2.226, 95%CI: 1.170–4.235, p = 0.015), and ADV (OR: 2.035, 95%CI: 1.105–3.750, p = 0.023) were identified as independent risk factors for SMPP. Conclusions: These findings highlight post-NPI shifts in MP epidemiology and identify ADV, InfB, and HPIV as early warning markers for SMPP. Full article
(This article belongs to the Special Issue Respiratory Viral Pathogenesis and Host-Microbe Crosstalk: From Bench to Bedside)
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9 pages, 1385 KB  
Article
Prevalence and Genetic Diversity of Torque teno felis virus (FcTTV) in Domestic Cats from Kazakhstan
by Gulzhan Yessembekova, Bolat Abdigulov, Alexandr Shevtsov, Asylulan Amirgazin, Sarsenbay Abdrakhmanov, Elena Shevtsova, Symbat Bolysbekkyzy, Salima Baduanova and Alexandr Shustov
Viruses 2025, 17(9), 1265; https://doi.org/10.3390/v17091265 - 19 Sep 2025
Viewed by 286
Abstract
Anelloviruses have a broad mammalian host range, including Torque teno felis virus (FcTTV), a felid-associated member that remains undercharacterized. This is the first comprehensive study of FcTTV in domestic cats in Central Asia. We analyzed blood samples from 206 domestic cats from the [...] Read more.
Anelloviruses have a broad mammalian host range, including Torque teno felis virus (FcTTV), a felid-associated member that remains undercharacterized. This is the first comprehensive study of FcTTV in domestic cats in Central Asia. We analyzed blood samples from 206 domestic cats from the large city of Astana, Kazakhstan, collected in 2023–2024. Using nested PCR we identified 63 FcTTV-positive samples (30.6% prevalence), and the sequences were compared to global reference strains. Potential demographic associations (sex and age) were assessed. The study revealed an overall FcTTV prevalence of 30.6%. Infection rates showed no significant sex-related differences: ages varied 4–168 months. ORF1 sequencing revealed multiple FcTTV variants in 27% of samples, with no demographic links. Phylogenetic analysis revealed distinct patterns at both nucleotide and amino acid levels: 3 groups of nucleotide sequences (max divergence 21.68%; intra-cluster 5.15–6.8%), and 3 clusters of amino acid sequences (max divergence 16.81%; intra-cluster 2.82–6.68%). Deletions were found in ORF1 in some variants. Global phylogeny aligned clusters with Asian/European strains (90–98% identity), confirming FcTTV1 affiliation and inter-regional transmission. Our study of FcTTV in Kazakhstan reveals moderate virus prevalence with considerable genetic diversity across viral strains and frequent co-infections with multiple variants. Full article
(This article belongs to the Section Animal Viruses)
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16 pages, 2686 KB  
Article
Rapid Visual Detection of Senecavirus A Based on RPA-CRISPR/Cas12a System with Canonical or Suboptimal PAM
by Xinrui Zhao, Genghong Jiang, Qinyi Ruan, Yunjie Qu, Xiaoyu Yang, Yongyan Shi, Dedong Wang, Jianwei Zhou, Jue Liu and Lei Hou
Viruses 2025, 17(9), 1264; https://doi.org/10.3390/v17091264 - 18 Sep 2025
Viewed by 253
Abstract
Senecavirus A (SVA) is an emerging pathogen responsible for vesicular lesions and neonatal mortality in swine. In the absence of effective vaccines or therapeutics, early and accurate diagnosis is essential for controlling SVA outbreaks. Although nucleic acid-based detection methods are commonly employed, there [...] Read more.
Senecavirus A (SVA) is an emerging pathogen responsible for vesicular lesions and neonatal mortality in swine. In the absence of effective vaccines or therapeutics, early and accurate diagnosis is essential for controlling SVA outbreaks. Although nucleic acid-based detection methods are commonly employed, there remains a pressing need for rapid, convenient, highly sensitive, and specific diagnostic tools. Here, we developed a two-pot assay combining recombinase polymerase amplification (RPA) with CRISPR/Cas12a containing crRNA targeting canonical protospacer adjacent motifs (PAMs) for simple, rapid, and visual identification of SVA in clinical samples. Subsequently, we successfully streamlined this system into a one-pot assay by selecting a specially designed crRNA targeting suboptimal PAM and integrating RPA amplification reagents and CRISPR/Cas12a detection components into a single reaction system in one tube. The developed methods exhibited diagnostic specificity, showing no cross-reactivity with four major swine viruses, while showing remarkable sensitivity with a lower detection limit of just two copies. Clinical validation in field samples using these two methods revealed perfect agreement (100% concordance) with conventional quantitative PCR (qPCR) results (sample size, n = 28), with both assays completing detection within 30 min. These results demonstrate that both the one-pot and two-pot RPA-CRISPR/Cas12a assays offer a reliable and efficient method for detecting SVA in this pilot study. Despite the limited sample size, the assays combine rapid reaction time with high sensitivity and specificity, showing great potential for future diagnostic applications. Full article
(This article belongs to the Section General Virology)
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10 pages, 2337 KB  
Article
Neutral Impact of SARS-CoV-2 Coinfection on the Recombination-Driven Evolution of Endemic HCoV-OC43
by Xueling Zheng, Yinyan Zhou, Yue Yu, Shi Cheng, Feifei Cao, Zhou Sun, Jun Li and Xinfen Yu
Viruses 2025, 17(9), 1263; https://doi.org/10.3390/v17091263 - 18 Sep 2025
Viewed by 199
Abstract
Knowledge gaps exist on whether SARS-CoV-2 co-infection alters recombination frequency or induces phylogenetic incongruities in endemic β-coronaviruses (HCoV-OC43, HCoV-HKU1), limiting our understanding of cross-species evolution. Among 7213 COVID-19 and 1590 non-COVID-19 acute respiratory cases (2021–2022) screened via multiplex PCR, β-coronavirus co-infections (SARS-CoV-2 + [...] Read more.
Knowledge gaps exist on whether SARS-CoV-2 co-infection alters recombination frequency or induces phylogenetic incongruities in endemic β-coronaviruses (HCoV-OC43, HCoV-HKU1), limiting our understanding of cross-species evolution. Among 7213 COVID-19 and 1590 non-COVID-19 acute respiratory cases (2021–2022) screened via multiplex PCR, β-coronavirus co-infections (SARS-CoV-2 + HCoV-OC43/HKU1) and single HCoV-OC43/HKU1 infections were identified. Whole-genome sequencing (Illumina NovaSeq) was performed. Phylogenies were reconstructed using Bayesian inference (MrBayes). Recombination was assessed via Bootscan analysis (SimPlot). Co-infection prevalence was low (0.51%, mainly HCoV-HKU1: 0.28%, HCoV-OC43: 0.11%). HCoV-OC43 diverged into lineage 1 (genotype K) and a novel recombinant lineage 2 (genotypes F/J/G/I segments), exhibiting accelerated evolution. HCoV-HKU1 remained genetically stable (genotype B). Co-infection status did not influence evolutionary outcomes. While SARS-CoV-2 co-infection may favor transmission of endemic HCoVs, their evolution appears driven by population-level selection, not co-infection. HCoV-OC43 underwent recombination-driven diversification, contrasting sharply with HCoV-HKU1’s stasis, highlighting distinct evolutionary strategies. Integrated genomic and clinical surveillance is critical for tracking coronavirus adaptation. Full article
(This article belongs to the Special Issue COVID-19 Complications and Co-infections)
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20 pages, 638 KB  
Review
Porcine Parvovirus in China: Recent Advances, Epidemiology, and Vaccine Strategies
by Yunchao Liu, Yumei Chen, Yanli Shang, Xiuli Deng and Huifang Hao
Viruses 2025, 17(9), 1262; https://doi.org/10.3390/v17091262 - 18 Sep 2025
Viewed by 374
Abstract
Porcine parvovirus (PPV), a non-envelope single-stranded DNA virus, causes severe reproductive disorders in swine worldwide, characterized by fetal mortality, mummification, and reduced boar fertility. As a highly prevalent pathogen in Chinese swine herds, PPV imposes substantial economic burdens on intensive pig production systems. [...] Read more.
Porcine parvovirus (PPV), a non-envelope single-stranded DNA virus, causes severe reproductive disorders in swine worldwide, characterized by fetal mortality, mummification, and reduced boar fertility. As a highly prevalent pathogen in Chinese swine herds, PPV imposes substantial economic burdens on intensive pig production systems. This review systematically synthesizes recent advances in PPV virology, focusing on genomic evolution of emerging strains (PPV1–PPV8), epidemiological dynamics of emerging strains, molecular pathogenesis, and novel diagnostic tools. Furthermore, we critically evaluate current vaccine strategies, highlighting their limitations in cross-protective efficacy and viral shedding control. By integrating multi-omics insights with immunological profiling, this work delineates actionable pathways for next-generation vaccine design and proposes a roadmap for rational antigen selection. This review consolidates foundational knowledge and establishes a translational bridge between basic virology and prevention and control of porcine parvovirus, addressing critical gaps in porcine reproductive disease management. Full article
(This article belongs to the Section Animal Viruses)
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16 pages, 3272 KB  
Article
Predicted Structures of Ceduovirus Adhesion Devices Highlight Unique Architectures Reminiscent of Bacterial Secretion System VI
by Adeline Goulet, Jennifer Mahony, Douwe van Sinderen and Christian Cambillau
Viruses 2025, 17(9), 1261; https://doi.org/10.3390/v17091261 - 18 Sep 2025
Viewed by 239
Abstract
Bacteriophages, or phages, are sophisticated nanomachines that efficiently infect bacteria. Their infection of lactic acid bacteria (LAB) used in fermentation can lead to significant industrial losses. Among phages that infect monoderm bacteria, those with siphovirion morphology characterized by a long, non-contractile tail are [...] Read more.
Bacteriophages, or phages, are sophisticated nanomachines that efficiently infect bacteria. Their infection of lactic acid bacteria (LAB) used in fermentation can lead to significant industrial losses. Among phages that infect monoderm bacteria, those with siphovirion morphology characterized by a long, non-contractile tail are predominant. The initial stage of phage infection involves precise host recognition and binding. To achieve this, phages feature host adhesion devices (HADs) located at the distal end of their tails, which have evolved to recognize specific proteinaceous or saccharidic receptors on the host cell wall. Ceduovirus represents a group of unique lytic siphophages that specifically infect the LAB Lactococcus lactis by targeting proteinaceous receptors. Despite having compact genomes, most of their structural genes are poorly annotated and the architecture and function of their HADs remain unknown. Here we used AlphaFold3 to explore the Ceduovirus HADs and their interaction with the host. We show that Ceduovirus HADs exhibit unprecedented features among bacteriophages infecting Gram+, share structural similarities with bacterial secretion system VI, and combine both saccharide and protein-binding modules. Moreover, we could annotate the majority of Ceduovirus genes encoding structural proteins by leveraging their predicted structures, highlighting AlphaFold’s significant contribution to phage genome annotation. Full article
(This article belongs to the Section Bacterial Viruses)
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15 pages, 5292 KB  
Article
Structural and Functional Characterization of Porcine Adeno-Associated Viruses
by Austin Nelson, Mario Mietzsch, Jane Hsi, Julia Eby, Paul Chipman and Robert McKenna
Viruses 2025, 17(9), 1260; https://doi.org/10.3390/v17091260 - 18 Sep 2025
Viewed by 326
Abstract
Current gene therapy treatments utilizing adeno-associated virus (AAV) vectors are based on capsids of primate origin. However, pre-existing neutralizing anti-AAV antibodies, that are present in a significant portion of the population, can lead to vector inactivation and reduced therapeutic efficacy. Advances in DNA [...] Read more.
Current gene therapy treatments utilizing adeno-associated virus (AAV) vectors are based on capsids of primate origin. However, pre-existing neutralizing anti-AAV antibodies, that are present in a significant portion of the population, can lead to vector inactivation and reduced therapeutic efficacy. Advances in DNA sequencing have facilitated the discovery of many AAVs from non-primate species, including isolates from pigs, which exhibit up to 50% capsid protein sequence divergence, compared to primate AAV serotypes. In this study, AAVs isolated from porcine tissues (AAVpo.1 and AAVpo.6) were selected for structural characterization due to their low capsid protein VP1 sequence identity compared to each other and to AAV9. The AAV vectors were produced via the standard triple transfection system in HEK293 cells using AAV2 rep to package AAV2-ITR vector genomes and were purified by iodixanol density gradient ultracentrifugation. The capsid structures of AAVpo.1 and AAVpo.6 were determined using cryo-electron microscopy and then compared to each other in addition to the AAV5 and AAV9 structures. Given that porcine AAVpo.6 has been reported to infect human cells and the ability to cross the blood–brain barrier, the functional characterization was focused on the identification of a potential glycan receptor utilized by the porcine capsids. Additionally, the porcine AAV capsid reactivity to human derived anti-AAV antibodies was assessed to evaluate the potential for these capsids to be used as alternative vectors for gene therapy, particularly for patients with pre-existing immunity to primate-derived AAV serotypes. Full article
(This article belongs to the Special Issue Porcine Viruses 2025)
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15 pages, 966 KB  
Article
Comparative Performance of Digital PCR and Real-Time RT-PCR in Respiratory Virus Diagnostics
by Irene Bianconi, Giovanna Viviana Pellecchia, Elisabetta Maria Incrocci, Fabio Vittadello, Maira Nicoletti and Elisabetta Pagani
Viruses 2025, 17(9), 1259; https://doi.org/10.3390/v17091259 - 18 Sep 2025
Viewed by 265
Abstract
Background: Respiratory viral infections pose a major global health burden, and molecular diagnostics such as Real-Time RT-PCR have revealed frequent co-infections. However, precise quantification of viral RNA remains challenging. Digital PCR (dPCR) offers absolute quantification without standard curves and may improve diagnostic [...] Read more.
Background: Respiratory viral infections pose a major global health burden, and molecular diagnostics such as Real-Time RT-PCR have revealed frequent co-infections. However, precise quantification of viral RNA remains challenging. Digital PCR (dPCR) offers absolute quantification without standard curves and may improve diagnostic accuracy. This study compares dPCR and Real-Time RT-PCR in detecting and quantifying influenza A, influenza B, respiratory syncytial virus (RSV), and SARS-CoV-2 during the 2023–2024 tripledemic. Methods: A total of 123 respiratory samples were analysed and stratified by cycle threshold (Ct) values into high, medium, and low viral load categories. Both dPCR and Real-Time RT-PCR were used to quantify and compare viral loads across these categories. Results: dPCR demonstrated superior accuracy, particularly for high viral loads of influenza A, influenza B, and SARS-CoV-2, and for medium loads of RSV. It showed greater consistency and precision than Real-Time RT-PCR, especially in quantifying intermediate viral levels. Conclusions: These findings highlight the potential of dPCR to enhance respiratory virus diagnostics and support a better understanding of co-infection dynamics. Nonetheless, its routine implementation is currently limited by higher costs and reduced automation compared to Real-Time RT-PCR. Full article
(This article belongs to the Section General Virology)
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14 pages, 2149 KB  
Article
Molecular Detection of Yellow Fever Virus in Haemagogus janthinomys Mosquitoes (Diptera: Culicidae) in a Rural Settlement in the State of Pará, Brazilian Amazon, 2024
by Joaquim Pinto Nunes Neto, Daniel Damous Dias, Bruna Laís Sena do Nascimento, Sandro Patroca da Silva, Sâmia Luzia Sena da Silva, Lúcia Aline Moura Reis, Hanna Carolina Farias Reis, Fábio Silva da Silva, Lucas Henrique da Silva e Silva, Durval Bertram Rodrigues Vieira, Roberto Carlos Feitosa Brandão, Wallace Oliveira Rosário, Francisco Amilton dos Santos Paiva, José Wilson Rosa Júnior, Bruno Tardelli Diniz Nunes, Lívia Carício Martins, Lívia Medeiros Neves Casseb and Ana Cecília Ribeiro Cruz
Viruses 2025, 17(9), 1258; https://doi.org/10.3390/v17091258 - 18 Sep 2025
Viewed by 356
Abstract
Yellow fever (YF) is an acute and potentially fatal hemorrhagic disease caused by the Yellow Fever virus (YFV), endemic to sub-Saharan Africa and several tropical countries, including Brazil. In Brazil, the Amazon region is considered the main endemic area. YFV is maintained in [...] Read more.
Yellow fever (YF) is an acute and potentially fatal hemorrhagic disease caused by the Yellow Fever virus (YFV), endemic to sub-Saharan Africa and several tropical countries, including Brazil. In Brazil, the Amazon region is considered the main endemic area. YFV is maintained in a sylvatic cycle involving Neotropical primates and mosquitoes of the genera Haemagogus and Sabethes, acting as primary and secondary vectors, respectively. In March 2024, entomovirological surveillance was conducted in Santa Bárbara do Pará, Pará, Brazil. A total of 286 mosquitoes were collected, classified into 13 species across nine genera, and grouped into 33 pools. Seventeen pools were tested by RT-qPCR for Orthoflavivirus (YFV, DENV, WNV, SLEV), Alphavirus (CHIKV, MAYV), and Orthobunyavirus (OROV). YFV was detected in four Haemagogus janthinomys pools, with Ct values ranging from 22.2 to 27.9. Metagenomic sequencing confirmed the presence of YFV with assigned reads and >99% protein identity. Notably, the detection occurred without human cases or primate deaths, enabling timely vaccination of the local population. These findings confirm YFV circulation in forested areas of the Belém metropolitan region and reaffirm Hg. janthinomys as a key vector. Our study reinforces the relevance of early entomovirological surveillance and preventive strategies, such as vaccination, to mitigate yellow fever reemergence. Full article
(This article belongs to the Section Animal Viruses)
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6 pages, 317 KB  
Commentary
Mpox Epidemics: A Call to Restore Humanity’s Lost Herd Immunity to Orthopoxviruses
by Misaki Wayengera, Henry Kyobe-Bosa, Winters Muttamba, Olushayo Oluseun Olu, Abdou Salam Gueye, Nicaise Ndembi, Neema Kamara, Morenike Oluwatoyin Folayan, Bruce Kirenga, Sitong Luo, Qingyu Li and Chikwe Ihekweazu
Viruses 2025, 17(9), 1257; https://doi.org/10.3390/v17091257 - 18 Sep 2025
Viewed by 307
Abstract
Global efforts to eradicate smallpox—an Orthopoxvirus infection—began in the mid-20th century, with the last naturally occurring case reported in 1977. This was achieved through global solidarity efforts that expanded the smallpox eradication vaccination program. Approximately 50 years following the cessation of mass smallpox [...] Read more.
Global efforts to eradicate smallpox—an Orthopoxvirus infection—began in the mid-20th century, with the last naturally occurring case reported in 1977. This was achieved through global solidarity efforts that expanded the smallpox eradication vaccination program. Approximately 50 years following the cessation of mass smallpox vaccination and in the absence of access to a sustainable boosting program, the population immunologically naïve to Orthopoxviruses has increased significantly. With increasing global movements and travels, we argue that the emergence of two back-to-back yet distinct mpox epidemics in the 21st century is a sign of humanity’s lost herd immunity to Orthopoxviruses. This needs concerted efforts to restore. Full article
(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)
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18 pages, 817 KB  
Review
BK Polyomavirus-Associated Nephropathy and Hemorrhagic Cystitis in Transplant Recipients—What We Understand and What Remains Unclear
by Tang-Her Jaing, Yi-Lun Wang and Tsung-Yen Chang
Viruses 2025, 17(9), 1256; https://doi.org/10.3390/v17091256 - 17 Sep 2025
Viewed by 387
Abstract
The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review [...] Read more.
The reactivation of BK polyomavirus (BKPyV) during severe immunosuppression plays a crucial role in two significant syndromes observed in transplant recipients: BK polyomavirus-associated nephropathy (BKPyVAN) in kidney transplant patients and BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) in hematopoietic cell transplant (HCT) recipients. This review aims to summarize the current understanding and lingering ambiguity by looking at three primary questions: (1) In cases with BKPyV-related illnesses in transplant patients, which diagnostic methods have the best track record of accuracy and success? (2) Which therapy approaches have the best track records of safety and efficacy in real-world clinical settings? (3) What can immunological research teach us about the development of future tailored treatments? Diagnosis involves the patient’s appearance, ruling out other potential causes, and employing quantitative PCR to identify active viral replication in urine or plasma. BKPyV-HC can vary from self-limited hematuria to potentially fatal bleeding, while BKPyVAN may lead to loss and dysfunction of the allograft. Reducing immunosuppression remains the key aspect of treatment. However, the effectiveness of antivirals (such cidofovir and leflunomide) is not always the same, and supporting measures depend on the syndrome. Researchers are looking into new immunotherapies, such as virus-specific cytotoxic T cells. Due to the intricate viro-immunopathology and lack of defined treatment regimens, future initiatives should focus on prospective studies to establish validated thresholds, enhance management algorithms, and integrate immune surveillance into individualized therapy. Full article
(This article belongs to the Special Issue Viral Immunology in Transplant Patients)
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23 pages, 2132 KB  
Review
Hot and Cold HCC: Uncoupling Viral Oncogenesis and Therapy
by Laura Sneller, Keshav Mathur, Shyam Kottilil and Poonam Mathur
Viruses 2025, 17(9), 1255; https://doi.org/10.3390/v17091255 - 17 Sep 2025
Viewed by 478
Abstract
Hepatocellular carcinoma (HCC) is rising in incidence globally. It is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. Infection with hepatitis B and/or C virus is a significant risk factor for developing HCC. These viruses exert their [...] Read more.
Hepatocellular carcinoma (HCC) is rising in incidence globally. It is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. Infection with hepatitis B and/or C virus is a significant risk factor for developing HCC. These viruses exert their carcinogenicity in both direct and indirect ways, including induction of immune exhaustion with prolonged antigen exposure. Therefore, the best therapeutic option for HCC is prevention, i.e., Hepatitis B vaccination and treatment of viral hepatitis. However, when HCC develops because of viral hepatitis or other etiologies, long-lasting effects on the immune system remain even after viral suppression, which affect the response to HCC therapy. Recent studies have suggested a “hot” and “cold” model for HCC, in which the two kinds of HCC tumors have very distinct tumor microenvironments. The microenvironment for hot HCC makes these tumors amenable to immunotherapy with checkpoint inhibitors. Therefore, converting cold HCC tumors to hot tumors may make them susceptible to immunotherapy. In this review, we provide an overview of HCC epidemiology and prevention, an overview of tumor microenvironments of hot and cold HCC, the proposed mechanisms for converting cold tumors to hot tumors, and a concise summary of the evidence for combination checkpoint inhibitor therapy for HCC. Full article
(This article belongs to the Special Issue Translational Research in Virology)
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