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Viruses
Volume 17
Issue 11
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Viruses, Volume 17, Issue 11 (November 2025) – 122 articles

Cover Story (view full-size image): The picornavirus 3C protease is essential for viral polyprotein processing and for hijacking host pathways to support virion production. It also binds the viral RNA genome to coordinate replication and translation. To probe the sequence and structural features governing these interactions, we examined a diverse panel of RNA oligonucleotides. Two RNA-binding sites on 3C were identified, confirming the known region and revealing a secondary site near the protease active site. Surprisingly, RNA engagement triggered liquid–liquid phase separation (LLPS), likely due to 3C’s ability to interact with multiple RNA strands simultaneously. This behavior suggests that 3C and its precursor 3CD may help regulate LLPS-driven assemblies, such as stress granules, during infection. View this paper
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9 pages, 729 KB  
Article
Pathogenesis and Transmissibility of Middle East Respiratory Syndrome Coronaviruses of African Origin in Alpacas
by Richard A. Bowen, Airn Hartwig, Anneliese Bruening, Audrey Walker and Malik Peiris
Viruses 2025, 17(11), 1524; https://doi.org/10.3390/v17111524 - 20 Nov 2025
Viewed by 425
Abstract
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) remains a highly significant threat to global public health. Dromedary camels are the zoonotic source of human infection. All cases of zoonotic Middle East Respiratory Syndrome (MERS) have occurred in Middle Eastern countries despite MERS-CoV infection [...] Read more.
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) remains a highly significant threat to global public health. Dromedary camels are the zoonotic source of human infection. All cases of zoonotic Middle East Respiratory Syndrome (MERS) have occurred in Middle Eastern countries despite MERS-CoV infection of camels being widespread in Africa. This disparity in the geographic burden of the disease may be due to genomic differences between MERS-CoV circulating in Middle Eastern countries (clades A and B) versus those infecting camels in Africa (clade C), although the precise genetic determinants of virulence remain to be elucidated. The objective of the studies reported here was to evaluate differences in the magnitude of virus shedding and in transmissibility of clades A/B and C viruses using alpacas as a surrogate for dromedary camels. We found that two of three African-origin, clade C strains of MERS-CoV induced very reduced levels of virus shedding and were transmitted inefficiently to contact control animals as compared to one other clade C virus and representative viruses from clade A and B. Lower virus titers in the nasopharynx may be associated with lower zoonotic transmission and human disease severity and may explain the observed epidemiology of MERS-CoV in Africa where zoonotic disease appears rare. These results add to our understanding of the transmission of different lineages of MERS CoV in camelids and zoonotic transmission. Full article
(This article belongs to the Section Coronaviruses)
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15 pages, 940 KB  
Article
Epstein–Barr Virus Load in the Saliva of Patients with Oropharyngeal Cancer—Could It Have Prognostic Significance?
by Karol Paradowski, Magdalena Góralczyk, Bartłomiej Drop, Mirosław Jarosz and Małgorzata Polz-Dacewicz
Viruses 2025, 17(11), 1523; https://doi.org/10.3390/v17111523 - 20 Nov 2025
Viewed by 535
Abstract
The discovery of EBV over 60 years ago was a breakthrough in understanding the development of many cancers, including head and neck cancers, but many processes remain to be explained. Scientists, looking for new biomarkers, have recently been paying a lot of attention [...] Read more.
The discovery of EBV over 60 years ago was a breakthrough in understanding the development of many cancers, including head and neck cancers, but many processes remain to be explained. Scientists, looking for new biomarkers, have recently been paying a lot of attention to salivary EBV DNA load. Oral EBV DNA load may indicate not only EBV lytic replication activity but also potentially correlate with EBV-related disease progression. Numerous studies indicate that saliva may be an alternative clinical material for both early diagnosis and prognosis of head and neck cancer (HNC). Therefore, we assessed salivary EBV DNA in oropharyngeal cancer patients (OPSCC). We observed that the EBV DNA level was higher in the group of EBV-positive OPSCC than in EBV-negative subjects and was also higher in more advanced clinical stages. In addition, the salivary EBV DNA load was positively correlated with the concentration of anti-EBV antibodies, MMP3, MMP9, and NF-κB. The ROC analysis confirmed the diagnostic accuracy of salivary EBV DNA load. Our preliminary results indicate the usefulness of determining EBV DNA load in saliva as a non-invasive prognostic biomarker in EBV-positive oropharyngeal cancer, but confirmation in larger cohort studies is required. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Viral Infection)
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16 pages, 5893 KB  
Article
Development of a Mass Antiviral Screening System Using Viral Hemorrhagic Septicemia Virus as an RNA Surrogate and Activity Confirmation with a Fish Rhabdovirus
by Ji Woo Shin, Su Yeon Kim, Min Jeong Kim, Taek-Kyun Lee and Tae-Jin Choi
Viruses 2025, 17(11), 1522; https://doi.org/10.3390/v17111522 - 20 Nov 2025
Viewed by 486
Abstract
With emerging viruses and drug resistance on the rise, the discovery and development of innovative antiviral substances and agents are necessary for the effective treatment and control of viral outbreaks. Surrogate viruses are safer alternatives used in research to mimic dangerous or hard-to-culture [...] Read more.
With emerging viruses and drug resistance on the rise, the discovery and development of innovative antiviral substances and agents are necessary for the effective treatment and control of viral outbreaks. Surrogate viruses are safer alternatives used in research to mimic dangerous or hard-to-culture viruses. They enable efficient, ethical, and cost-effective screening of antiviral compounds. In this study, we used a recombinant viral hemorrhagic septicemia virus (rVHSV) expressing enhanced green fluorescent protein as a surrogate for RNA viruses for the high-throughput screening of antiviral agents. An optimized mixture of viruses and EPC host cells was distributed in 96-well plates containing chemical compounds or plant extracts for screening. Using this system, 44,642 chemical compounds and 8104 plant and marine organism extracts were tested; 140 candidates were selected from primary screening, and 8 compounds and 5 plant extracts were further selected based on the selectivity index (SI), representing the ratio of the cytotoxic concentration (CC50) to the inhibition concentration (IC50). Among these, compound 3, which had the highest SI value of 1046, was further tested, considering in vitro activity against VHSV and another fish rhabdovirus, snakehead rhabdovirus (SHRV). Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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26 pages, 2570 KB  
Article
Five Years of COVID-19 in Tocantins, Brazil: Epidemiology, Vaccination Impact, and SARS-CoV-2 Genomic Dynamics (2020–2025)
by Olivia de Souza da Conceição, Ueric José Borges de Souza, Franciano Dias Pereira Cardoso, Evgeni Evgeniev Gabev, Bergmann Morais Ribeiro, Gil Rodrigues dos Santos, Renisson Neponuceno de Araújo Filho, Marcos Gontijo da Silva, Fernando Rosado Spilki and Fabrício Souza Campos
Viruses 2025, 17(11), 1521; https://doi.org/10.3390/v17111521 - 20 Nov 2025
Viewed by 837
Abstract
The coronavirus disease 2019 (COVID-19) pandemic in Tocantins, Brazil, exhibited distinct phases between 2020 and 2025, with high mortality concentrated in 2020–2021 and subsequent stabilization at residual levels. Using epidemiological data, statistical modeling, and genomic surveillance, we show that the crisis peaked in [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic in Tocantins, Brazil, exhibited distinct phases between 2020 and 2025, with high mortality concentrated in 2020–2021 and subsequent stabilization at residual levels. Using epidemiological data, statistical modeling, and genomic surveillance, we show that the crisis peaked in 2021, coinciding with the circulation of Gamma and Delta, when health system capacity was severely strained. From 2022 onwards, the spread of Omicron led to record incidence but proportionally low mortality, reflecting accumulated immunity, vaccination, and improved clinical management. Vaccination represented the turning point, reducing hospitalizations and deaths by over 90% and driving a clear decoupling between incidence and severity. Interrupted time-series and generalized additive model (GAM) analyses confirmed sustained reductions in transmission and severity associated with mass immunization. Genomic sequencing of 3941 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes identified 166 lineages and successive variant replacements, culminating in the predominance of LP.8.1.4 in 2025. To our knowledge, this is one of the few integrated, long-term analyses (2020–2025) combining epidemiological and genomic data, capturing the full succession of variants up to LP.8.1.4 and highlighting Tocantins as a strategic “variant corridor” linking Brazil’s North and Central-West regions. These findings underscore the dual role of vaccination and genomic surveillance in shaping the epidemic trajectory and the importance of sustaining both strategies to mitigate future health crises. Full article
(This article belongs to the Section Coronaviruses)
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1 pages, 132 KB  
Correction
Correction: Agundis-Tinajero et al. Deep Learning-Based Automatic Segmentation and Analysis of Mitochondrial Damage by Zika Virus and SARS-CoV-2. Viruses 2025, 17, 1272
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(11), 1520; https://doi.org/10.3390/v17111520 - 20 Nov 2025
Viewed by 265
Abstract
In the original publication [1], Figure 1b was previously published by the authors in the PLoS One, but the citation (reference 14) was inadvertently omitted [...] Full article
6 pages, 564 KB  
Obituary
Tribute to Philippe Gasque (1966–2024): From Complement Biology to Alphavirus Pathogenesis and Chikungunya Research
by Wildriss Viranaïcken, Gregorie Lebeau, Hoarau Jean-Jacques and Pascale Krejbich-Trotot
Viruses 2025, 17(11), 1519; https://doi.org/10.3390/v17111519 - 20 Nov 2025
Viewed by 458
Abstract
The passing of Professor Philippe Gasque on 11 July 2024 marked the loss of a prominent figure in immunology and infectious disease research [...] Full article
(This article belongs to the Section General Virology)
17 pages, 1610 KB  
Article
Isolation and Characterization of a Novel Thermostable Bacteriophage Targeting Multi-Drug-Resistant Salmonella Enteritidis
by Salman A. Almashtoub, Gabriel H. Fares, Tasnime A. Abdo Ahmad, Sara Barada, Ahmad Turk, Dayana Shoukair, Ghassan M. Matar and Esber S. Saba
Viruses 2025, 17(11), 1518; https://doi.org/10.3390/v17111518 - 19 Nov 2025
Viewed by 431
Abstract
(1) Background: The emergence of multidrug-resistant (MDR) Salmonella enterica poses a major threat to global public health, underscoring the urgent need for alternative therapeutic strategies. Bacteriophages represent a promising alternative due to their high specificity and potent ability to lyse MDR strains. (2) [...] Read more.
(1) Background: The emergence of multidrug-resistant (MDR) Salmonella enterica poses a major threat to global public health, underscoring the urgent need for alternative therapeutic strategies. Bacteriophages represent a promising alternative due to their high specificity and potent ability to lyse MDR strains. (2) Methods: In this study, we isolated a novel MDR Salmonella Enteritidis-targeting bacteriophage from Lebanese sewage and characterized its host range, thermal and pH stability, and infection dynamics. Whole-genome sequencing was performed using Illumina technology to determine its genetic features and taxonomic classification. (3) Results: the bacteriophage was classified within the genus Jerseyvirus and the class Caudoviricetes with a 43 kb dsDNA genome encoding 66 open reading frames (ORFs). It demonstrated remarkable thermal stability, retaining infectivity after prolonged incubation at 65 °C, and showed a broad host range. The phage formed large, clear plaques, displayed rapid adsorption (>97% within 3 min), a short latent period (20 min), and a burst size of ~32 PFU per cell. Genome analysis revealed no lysogeny, virulence, or resistance genes, confirming its strictly lytic nature and supporting its potential use as a biocontrol agent. (4) Conclusions: These findings identify SA01 as a novel, strictly lytic, and thermally stable bacteriophage with strong potential as a biocontrol agent against multidrug-resistant Salmonella Enteritidis. Its broad host range suggests potential activity also against other Salmonella enterica serovars, supporting its applicability in food safety and biotechnology. Full article
(This article belongs to the Special Issue Dual Nature of Bacteriophages: Friends or Enemies in Food Industry?)
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15 pages, 1588 KB  
Article
Cytokine and Antibody Isotype Responses in Vaccinated Healthcare Workers with SARS-CoV-2 Breakthrough Infections
by Miguel Ángel Fernández-Rojas, Tanya Plett-Torres, Guillermina Ávila, Mirza Romero-Valdovinos, Ana María Salazar, Monserrat Sordo, Mariana Chávez-Vargas, Cesar Josué Coeto Ángeles, Mayra Cruz-Rivera, Carlos Santiago-Olivares, Juan Pablo Ramírez Hinojosa, Pablo Maravilla, Patricia Ostrosky-Wegman, Fela Mendlovic and Ana Flisser
Viruses 2025, 17(11), 1517; https://doi.org/10.3390/v17111517 - 19 Nov 2025
Viewed by 901
Abstract
Background: Healthcare workers (HCWs) are at high risk of breakthrough SARS-CoV-2 infections despite complete vaccination schedules. There are gaps in our understanding of the specific antibody isotypes and cytokine profiles produced during an infection following vaccination. In this study, we evaluated SARS-CoV-2− [...] Read more.
Background: Healthcare workers (HCWs) are at high risk of breakthrough SARS-CoV-2 infections despite complete vaccination schedules. There are gaps in our understanding of the specific antibody isotypes and cytokine profiles produced during an infection following vaccination. In this study, we evaluated SARS-CoV-2−specific antibody isotypes and their association with cytokine production in HCWs with breakthrough infections. Methods: Serum samples from 114 HCWs were analyzed for antibody isotypes against the nucleoprotein (NCP) and the receptor binding domain (RBD) of the spike protein, as well as for a panel of 13 cytokines. Results: Vaccinated SARS-CoV-2+ HCWs showed a higher prevalence of anti-SARS-CoV-2 antibodies against NCP (IgM = 93.8%, IgG = 93.8%, IgA = 28.1%) and RBD (IgM = 46.9%, IgG = 100%, IgA = 90.6%). A specific IgM response to NCP was more frequent in vaccinated SARS-CoV-2+ individuals, whereas IgA responses were predominantly specific for RBD. Both pro- and anti-inflammatory cytokines were elevated in vaccinated HCWs with breakthrough infections compared with unvaccinated and uninfected individuals. Interestingly, infected IgG+ HCWs with IgM specific for both NCP and RBD exhibited significantly higher IL-8, IL-6, TNF-α, IFN-γ, IL-2, IL-10, and TGF-β concentrations. Conclusion. Our data show that breakthrough infections in vaccinated HCWs induce a robust pro-and anti-inflammatory cytokine profile, which is associated with a broader IgM response directed against both NCP and RBD. Full article
(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))
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17 pages, 1213 KB  
Article
Network Dynamics and Evolutionary Drivers of HIV Drug Resistance in Eastern China, from 2022 to 2024
by Dongqing Cao, Hui Xing, Yi Feng, Jiafeng Zhang, Liangkang Zhou, Zhuojing Jiang, Jinkun Chen and Tingting He
Viruses 2025, 17(11), 1516; https://doi.org/10.3390/v17111516 - 19 Nov 2025
Viewed by 444
Abstract
The increasing prevalence of HIV drug resistance poses a significant challenge. This study aimed to investigate the epidemiological dynamics and molecular characteristics of pretreatment drug resistance (PDR) and acquired drug resistance in Shaoxing, Eastern China. Methods: From 2022 to 2024, 571 newly diagnosed [...] Read more.
The increasing prevalence of HIV drug resistance poses a significant challenge. This study aimed to investigate the epidemiological dynamics and molecular characteristics of pretreatment drug resistance (PDR) and acquired drug resistance in Shaoxing, Eastern China. Methods: From 2022 to 2024, 571 newly diagnosed HIV-infected individuals and 119 individuals with antiretroviral treatment failure were enrolled. Molecular transmission networks and Bayesian analysis were employed to identify key drug-resistant clusters and trace their origins. Results: The overall PDR prevalence was 14.4% (85/571). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 9.8% (56/571), significantly higher than to NRTIs (1.1%, 6/571) and PIs (3.7%, 21/571) (χ2 = 50.014, p < 0.001). Molecular network analysis identified large clusters harboring K103N and Q58E resistance mutations within the CRF07_BC subtype. Bayesian analysis estimated their introduction into Shaoxing from Guangdong Province around 2016 and 2017, respectively. Integrated network analysis revealed close linkages between virological failure and newly diagnosed cases, highlighting the role of treatment failure in resistance transmission. Conclusion: Targeted interventions against specific subtypes and transmission clusters, alongside continuous resistance surveillance, are essential to curb the spread of drug-resistant HIV and optimize ART regimens. Full article
(This article belongs to the Special Issue Molecular Insights into HIV-1 Infection)
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15 pages, 1506 KB  
Article
West Nile Virus Pilot Screening in Field-Collected Aedes japonicus (Theobald, 1901): An Update of Species Distribution in Poland, 2025
by Paweł Niemiec, Jowita Samanta Niczyporuk, Wojciech Kozdruń, Agnieszka Stolarek, Łukasz Mielczarek, Kamil Słomczyński, Kacper Barszcz, Paweł Kuziora, Grzegorz Jarosiewicz, Alicja Jarosz, Andrzej Józef Woźnica, Grzegorz Zaleśny, Mariusz Gwardjan, Gabriela Ochała-Gierek and Marcin Gierek
Viruses 2025, 17(11), 1515; https://doi.org/10.3390/v17111515 - 19 Nov 2025
Viewed by 722
Abstract
(1) Background: The Asian bush mosquito Aedes japonicus is an invasive species in Europe, including Poland. Given its laboratory-confirmed competence for West Nile virus (WNV) transmission and its detection as a WNV vector in field-collected mosquitoes, this study investigated whether Polish Aedes japonicus [...] Read more.
(1) Background: The Asian bush mosquito Aedes japonicus is an invasive species in Europe, including Poland. Given its laboratory-confirmed competence for West Nile virus (WNV) transmission and its detection as a WNV vector in field-collected mosquitoes, this study investigated whether Polish Aedes japonicus harbor WNV and aimed to update knowledge on its distribution in Poland. (2) Methods: In September 2024, 137 adult Aedes japonicus were collected from three suburban sites in Poland (Kielce, Mikołów, Kraków). Specimens were screened for WNV using RT-PCR and rRT-PCR. Additionally, unpublished records of Aedes japonicus were compiled to update the species’ distribution. (3) Results: No WNV genetic material was detected in field-collected mosquitoes in Poland. By 2025, Aedes japonicus had been recorded in half of Polish voivodeships, with most observations in Małopolskie, Śląskie, and Łódzkie. The largest adult populations occurred in Kielce. Ecological traits in Poland matched European and US data, including larval development in artificial containers, preference for suburban and forested habitats, and peak adult activity in late summer. (4) Conclusions: Although WNV was not detected, the rapid spread of Aedes japonicus in Poland underlines the need for continued monitoring of its distribution, population dynamics, and potential role in WNV transmission. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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15 pages, 1004 KB  
Article
Antenatal Screening for HTLV-1 and -2 Among Pregnant Women in Grenada: Combined Seroprevalence, Trends, and Public Health Implications (2015–2024)
by Sherry-Ann N. Joseph, Christine Richards, Yusuf Yakubu, Achut Malur and Tonia Frame
Viruses 2025, 17(11), 1514; https://doi.org/10.3390/v17111514 - 19 Nov 2025
Viewed by 481
Abstract
The prevalence of Human T-cell Lymphotropic Virus (HTLV) infections in Grenada has not been published since 2013. This study aimed to determine the combined seroprevalence and trends in HTLV-1 and HTLV-2 among pregnant women in Grenada from 2015 to 2024. Data were analyzed [...] Read more.
The prevalence of Human T-cell Lymphotropic Virus (HTLV) infections in Grenada has not been published since 2013. This study aimed to determine the combined seroprevalence and trends in HTLV-1 and HTLV-2 among pregnant women in Grenada from 2015 to 2024. Data were analyzed to determine the overall combined seroprevalence, observed trends, and public health implications over time. Data obtained from the Ministry of Health, Grenada, were analyzed to determine and compare the annual combined seroprevalence rate and the prevalence by age group and by health district during 2015–2024. Every pregnant woman included in the analysis was tested for HTLV-1 and -2 at the government’s public laboratories in Grenada. The overall rate of infection among persons tested was 1.45%. The highest prevalence of infection was among the 40+ (mature) age group. A significant association was found between HTLV infection and the mature age group (ϰ2 = 7.981, p = 0.017, OR = 2.6, 95% CI: 1.1559–5.7122). Pregnant women aged 40 years and over are 2.6 times more at risk of infection compared to pregnant adolescents. Trends were also observed by health district, in which the prevalence rate was the highest in St. Patrick (2.18%) and the lowest in St. George (0.95%). Although there were no statistically significant associations observed between HTLV and the COVID-19 pandemic, there is a need for further research to understand the impact of emergencies on HTLV screening and prevalence. Further studies are also needed to identify factors and modes of HTLV transmission. Overall, these findings underscore the importance of targeted surveillance and tailored interventions to address HTLV transmission risks and protect population health in Grenada. Full article
(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)
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15 pages, 1981 KB  
Article
Leveraging Classical Virology and High Throughput Sequencing for Viral Discovery Using a Historical Viral Collection
by Mark Sistrom, Matthew Neave, Ancy Joseph, Kim Newberry, Hannah Andrews, Cathy Shilton, Vidya Bhardwaj and Richard Weir
Viruses 2025, 17(11), 1513; https://doi.org/10.3390/v17111513 - 18 Nov 2025
Viewed by 554
Abstract
Northern Australia has long been a hotbed of arboviral discovery, and collections of viral isolates from Northern Australia represent an invaluable resource for both our knowledge of viral diversity and for disease preparedness and treatment. While discovery of novel viruses via classical virology [...] Read more.
Northern Australia has long been a hotbed of arboviral discovery, and collections of viral isolates from Northern Australia represent an invaluable resource for both our knowledge of viral diversity and for disease preparedness and treatment. While discovery of novel viruses via classical virology methods is on the decline, next generation sequencing offers the possibility to speed up viral discovery, albeit at the expense of the collection of valuable life history data. By sequencing unknown isolates from historical viral collections, we may leverage both the rich data collected through classical virology and the power of identification using contemporary sequencing technologies. In the present study, we sequenced 76 historical viral isolates held at the Berrimah Veterinary Laboratory in Darwin, northern Australia, for which serological typing had yielded ambiguous results. We determined that 43 of these isolates belong to the genera Hapavirus, Orbivirus, and Orthobunyavirus. Several of these isolates are putatively novel genotypes or potential taxa, which has significant potential implications for human and animal health. This study demonstrates the utility of historical collections for viral discovery and characterisation and how considerable past efforts to isolate and characterise viruses can be enhanced using next generation sequencing approaches. Full article
(This article belongs to the Section General Virology)
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17 pages, 1446 KB  
Article
Gonadocorticoids Have Different Effects on the Expression of Toll-like Receptors When Infected with Various HIV-1 Subtypes
by Marina Nosik, Konstantin Ryzhov, Elena Berezhnaya, Elizaveta Bystritskaya, Olga Lobach, Irina Kiseleva, Elizaveta Kostyuchenko, Anna Kuzina, Ekaterina Meremianina, Dmitry Kireev and Oxana Svitich
Viruses 2025, 17(11), 1512; https://doi.org/10.3390/v17111512 - 18 Nov 2025
Viewed by 361
Abstract
Recent studies suggest that immune response to pathogens may vary depending on changes in hormone levels. Toll-like receptors (TLRs) are the key components of the innate immune system and play a crucial role in HIV infection. Given the significant genetic diversity of HIV-1, [...] Read more.
Recent studies suggest that immune response to pathogens may vary depending on changes in hormone levels. Toll-like receptors (TLRs) are the key components of the innate immune system and play a crucial role in HIV infection. Given the significant genetic diversity of HIV-1, this study examined the effect of female sex hormones on the several TLR2, TLR4, and TLR9 expression in human peripheral blood mononuclear cells (PBLs) isolated from different female donors and infected with different variants of HIV-1 subtypes A6 and B. Thus, high doses of hormones upregulated the TLR2 and TLR9 expression in PBLs infected only with v1.A6, which also correlated with an increased viral load: by 3.8 times (p = 0.0033) when cells were treated with estradiol and by 4.4 times (p = 0.006) when treated with progesterone. Hormones did not modulate TLRs expression in the cells infected with subtype B, with the exception of one donor. In PBLs from this donor infected with the v1.B variant, hormones upregulated TLRs expression, which also correlated with the increased viral load (1.3-fold increase (p = 0.0036)). Hence, it was shown that gonadal steroids can play an important role in HIV-1 replication and immune response to a pathogen. Moreover, it was shown that different isolates of the same subtype may have distinct biological properties. The detected diversity in the TLRs expression in infected PBLs from different donors indicates that host genetics may also play an important role in HIV susceptibility. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction, 4th Edition)
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2 pages, 305 KB  
Correction
Correction: Jargalsaikhan et al. The Era of Gene Therapy: The Advancement of Lentiviral Vectors and Their Pseudotyping. Viruses 2025, 17, 1036
by Bat-Erdene Jargalsaikhan, Masanaga Muto and Masatsugu Ema
Viruses 2025, 17(11), 1511; https://doi.org/10.3390/v17111511 - 18 Nov 2025
Viewed by 311
Abstract
In the original publication [...] Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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13 pages, 467 KB  
Article
Infection-Induced Telomere Length Variation: Insights into Pathogenesis of Koala Retrovirus
by Hiu Ming Cheung, Sze Wing Jamie Lin, Hanh Thi Hong Nguyen, Tamsyn Stephenson, Natasha Speight and Farhid Hemmatzadeh
Viruses 2025, 17(11), 1510; https://doi.org/10.3390/v17111510 - 17 Nov 2025
Viewed by 444
Abstract
The pathogenesis of koala retrovirus (KoRV) has been explored in various contexts, yet its role in tumorigenesis remains incompletely understood. Unlike acute transforming retroviruses, KoRV lacks a viral oncogene but may contribute to oncogenesis via indirect mechanisms. However, the relationship between KoRV and [...] Read more.
The pathogenesis of koala retrovirus (KoRV) has been explored in various contexts, yet its role in tumorigenesis remains incompletely understood. Unlike acute transforming retroviruses, KoRV lacks a viral oncogene but may contribute to oncogenesis via indirect mechanisms. However, the relationship between KoRV and telomere length, as a potential indicator of telomerase activity, has not been examined. This study investigates the effect of KoRV infection on telomere length in 47 samples from Southern Australian koalas in a novel telomere length quantification method. Telomere lengths of 30 KoRV-negative samples were compared to those of 17 KoRV-positive samples using the Absolute Human Telomere Length Quantification qPCR kit (ScienCell Research Laboratories, California, USA). The telomere length in KoRV-infected WBCs was significantly longer than the uninfected ones (t = −2.059, p-value = 0.045). In line with this, telomere length correlated positively with proviral load (r = 0.421, p-value = 0.003), further linking viral burden to telomere elongation. Furthermore, the effect of age on telomere length differed by infection status (β = −5329.7, p-value = 0.0038); KoRV-positive individuals exhibited longer telomeres at a younger age but experienced more rapid telomere attrition over time compared to KoRV-negative individuals. These results suggest KoRV promotes telomerase elongation ability and modulates age-related telomere dynamics, potentially contributing to subsequent cellular immortality and oncogenesis. These pathways may overlap with other retroviruses, where telomerase dysregulation contributes to their oncogenic potential. This study provides new insights into KoRV pathogenesis and DNA quantification methodology, which could be valuable for future research by identifying predictive markers for tumour progression and potential therapeutic targets in affected koalas. Full article
(This article belongs to the Section Animal Viruses)
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16 pages, 476 KB  
Review
The Role of Saliva and Mouthwashes in the Detection and Reduction of Oral Viral Load: A Scoping Review
by Flavia Vitiello, Romain Lan, Giovanna Orsini, Denis Bourgeois and Florence Carrouel
Viruses 2025, 17(11), 1509; https://doi.org/10.3390/v17111509 - 17 Nov 2025
Viewed by 564
Abstract
Background: The oral cavity is an entry site and a reservoir for viruses. Viral particles accumulate in saliva, which serves as a diagnostic fluid and vehicle for transmission (droplets and aerosols). Antiseptic mouthwashes were proposed as adjunctive measures to temporarily reduce oral viral [...] Read more.
Background: The oral cavity is an entry site and a reservoir for viruses. Viral particles accumulate in saliva, which serves as a diagnostic fluid and vehicle for transmission (droplets and aerosols). Antiseptic mouthwashes were proposed as adjunctive measures to temporarily reduce oral viral load. Objectives: This scoping review aims to investigate the role of the oral cavity in viral infections, focusing on saliva and the use of antiseptic mouthwashes to reduce salivary viral load. Methods: Following the PRISMA-ScR guidelines, PubMed, EMBASE, and Web of Science were searched for human studies (2015–2025) investigating oral viral infections, saliva, or mouthwashes. Eligible studies were classified and analyzed for population, intervention, and outcomes. Results: Twenty-three studies met inclusion criteria (sixteen randomized controlled trials and seven systematic reviews). All included studies focused exclusively on SARS-CoV-2, as no clinical evidence on other oral viruses met the eligibility criteria. Saliva was consistently identified as a reliable, non-invasive specimen reflecting disease dynamics and transmission potential. Mouthwashes containing povidone-iodine, cetylpyridinium chloride, chlorhexidine, hydrogen peroxide or β-cyclodextrin–citrox produced measurable but short-lived reductions in salivary viral load. Heterogeneity and lack of standardized outcomes limited comparability. Conclusions: Antiseptic mouthwashes can provide a transient and complementary reduction in salivary viral load, particularly before aerosol-generating procedures; however, they should be regarded only as adjunctive measures and not as substitutes for standard infection-control protocols. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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20 pages, 2447 KB  
Article
Viromic Insights into Gut RNA Virus Diversity Among Three Corvid Species
by Yonggang Dong, Sitong Fan, Lilin Zhu, Kirill Sharshov and Wen Wang
Viruses 2025, 17(11), 1508; https://doi.org/10.3390/v17111508 - 17 Nov 2025
Viewed by 418
Abstract
As viromics advances, the diversity and ecological significance of RNA viruses in global ecosystems are gaining growing recognition. Nevertheless, studies on RNA viruses in wildlife, especially non-model avian species, are still relatively scarce. This study employed viral metagenomics to systematically characterize the gut [...] Read more.
As viromics advances, the diversity and ecological significance of RNA viruses in global ecosystems are gaining growing recognition. Nevertheless, studies on RNA viruses in wildlife, especially non-model avian species, are still relatively scarce. This study employed viral metagenomics to systematically characterize the gut RNA viromes of three widely distributed corvid species on the Qinghai–Tibet Plateau: the Red-billed chough (Pyrrhocorax pyrrhocorax), Daurian jackdaw (Coloeus dauuricus), and Rook (Corvus frugilegus). These three corvid species are closely associated with human-inhabited areas on the Qinghai–Tibet Plateau and display distinctive scavenging behaviors that may lower their exposure to environmental pathogens while concurrently elevating their risk of viral infection, rendering them key targets for viral surveillance and research into zoonotic disease transmission. The analysis annotated viral communities into 4 phyla and 8 classes, with Pisuviricota and Kitrinoviricota emerging as the predominant phyla in all samples. Alpha diversity analysis indicated no significant differences among groups, while beta diversity showed significant compositional differences. KEGG annotation revealed that enriched functional pathways were mainly concentrated in “Global and overview maps”, “Drug resistance: antimicrobial”, and “Biosynthesis of other secondary metabolites”. Furthermore, 4 antibiotic resistance genes and 13 putative virulence factor genes were identified. Phylogenetic analysis further indicated that several identified viruses have the potential for cross-species transmission, underscoring the pivotal role of wild birds in viral ecosystems and disease spread. This study uncovered multi-faceted features of the gut RNA viromes in the three crow species, spanning structural, functional, and evolutionary dimensions. These results offer novel perspectives on the viromes of wild corvids and their potential contributions to viral emergence and dissemination in the Qinghai–Tibet Plateau ecosystem. Full article
(This article belongs to the Special Issue Viral Surveillance, Transmission, Pathogenesis, and Vaccine Development in Domestic Animals and Wildlife)
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19 pages, 1793 KB  
Article
Seroprevalence of Arboviruses and Genetic Characterization of Orbiviruses in Sloths from Western Panama
by Rita Corrales, Yamilka Díaz, Vanessa Pineda, Yaneth Pitti, Lisseth Saenz, Jean-Paul Carrera, Celestino Aguilar, Alexander Martínez, Maria Chen-Germán, Kathryn A. Hanley, Nikos Vasilakis, Robert B. Tesh, Azael Saldaña and Sandra López-Vergès
Viruses 2025, 17(11), 1507; https://doi.org/10.3390/v17111507 - 17 Nov 2025
Viewed by 420
Abstract
Arthropod-borne viruses (arboviruses) are an increasingly significant threat to public health in tropical regions. In this study, we investigated the seroprevalence of various arboviruses in two species of sloth (Choloepus hoffmanni and Bradypus variegatus) in rural and peri-urban areas of Western [...] Read more.
Arthropod-borne viruses (arboviruses) are an increasingly significant threat to public health in tropical regions. In this study, we investigated the seroprevalence of various arboviruses in two species of sloth (Choloepus hoffmanni and Bradypus variegatus) in rural and peri-urban areas of Western Panama province. Between 2013 and 2018, blood samples from 60 sloths were tested for neutralizing antibodies against ten arboviruses. Significant variation in seroprevalence of different arboviruses was observed: 6.7% of sloths were seropositive for Madariaga virus, 6.7% for Venezuelan equine encephalitis virus, and 4.8% for Oropouche virus, while none were seropositive for dengue type 2, Zika, chikungunya, Una, Mayaro, or Punta Toro viruses. Notably, two Changuinola virus (CGLV) strains, which were previously isolated from Panamanian sloths in the 1970s, showed high seroprevalence: Pansloth 149 (23.3%) and D50 (53.3%). Given the high seroprevalence detected in our study and the lack of genomic characterization of the historical Pansloth 149 isolate, we performed next-generation sequencing of its complete genome using Illumina technology to understand its genetic diversity and evolutionary relationship with other CGLV strains. Full article
(This article belongs to the Special Issue One Health Approach: Tackling the Spillover of Zoonotic Viruses from Wildlife to Humans)
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14 pages, 2477 KB  
Article
Structural Analysis of Inhibitor Binding to the Feline Enteric Coronavirus (FECV) Main Protease
by Arooma Maryam, Stephanie A. Moquin, Dustin Dovala, Jagroop Kaur, Nese Kurt Yilmaz, Ala M. Shaqra and Celia A. Schiffer
Viruses 2025, 17(11), 1506; https://doi.org/10.3390/v17111506 - 16 Nov 2025
Viewed by 379
Abstract
Coronaviruses include various strains that reside in natural animal reservoirs, with zoonotic transmission posing risks to both domesticated animals and human health. Recent efforts to address coronavirus infections have focused on developing inhibitors targeting the main protease (Mpro), some of which [...] Read more.
Coronaviruses include various strains that reside in natural animal reservoirs, with zoonotic transmission posing risks to both domesticated animals and human health. Recent efforts to address coronavirus infections have focused on developing inhibitors targeting the main protease (Mpro), some of which exhibit potential broad-spectrum efficacy. This study presents crystal structures of four clinically relevant inhibitors—GC376, PF-00835231, nirmatrelvir, and ibuzatrelvir—bound to Mpro from the feline coronavirus strain FECV-UU23. Structural analysis identified distinct FECV-specific features within the active site where these inhibitors bind and revealed S4 loop as a susceptible structural region essential for the enhanced binding of inhibitors in UU23 Mpro. We therefore propose to incorporate sterically constrained, functionally tailored heterocyclic moieties at the P3 site of known inhibitors which can optimally engage Q187, P188, and S189 residues of the S4 loop. The findings presented enhance understanding of inhibitor specificity and reinforce the promise of these inhibitor scaffolds for developing antivirals against feline coronavirus strains, with possible applications in broad-spectrum coronavirus therapy. Full article
(This article belongs to the Special Issue 15-Year Anniversary of Viruses)
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26 pages, 2251 KB  
Article
Viral Coinfections Potentially Associated with Feline Chronic Gingivostomatitis in Cats with Feline Infectious Peritonitis
by Jennifer Wenk, Marina L. Meli, Solène M. Meunier, Sandra Felten, Celia C. de Witt Curtius, Aline Crespo Bouzon, Ilaria Cerchiaro, Benita Pineroli, Anja Kipar, Stefan Unterer, Katharina Zwicklbauer, Katrin Hartmann, Regina Hofmann-Lehmann and Andrea M. Spiri
Viruses 2025, 17(11), 1505; https://doi.org/10.3390/v17111505 - 15 Nov 2025
Viewed by 769
Abstract
Feline infectious peritonitis (FIP) is a fatal but now treatable disease in cats caused by feline coronavirus (FCoV). This study prospectively investigated viral coinfections in 100 cats diagnosed with FIP and subsequently treated with oral GS-441524 (Bova UK) and their influence on outcome, [...] Read more.
Feline infectious peritonitis (FIP) is a fatal but now treatable disease in cats caused by feline coronavirus (FCoV). This study prospectively investigated viral coinfections in 100 cats diagnosed with FIP and subsequently treated with oral GS-441524 (Bova UK) and their influence on outcome, focusing on viruses potentially associated with feline chronic gingivostomatitis (FCGS). Cats were tested for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline calicivirus (FCV), feline herpesvirus (FHV), feline foamy virus (FFV), and feline gammaherpesvirus (FcaGHV1). Coinfections were identified at the following frequencies: FCV (27), FFV (22), FHV (6), FIV (4), FcaGHV1 (2), and FeLV (2, both progressive infections). FFV infection was significantly associated with FIV (pF = 0.0021) and FHV (pF = 0.0226) infection. FCGS was present in 25/97 cats with FCV infection being associated with FCGS (pF = 0.0032); no significant associa-tions were found for the other viruses and FCGS. The 42-day oral GS-441524 treatment’s success rate was 94% (five cats died, one relapsed). Coinfections did not significantly influence disease severity or treatment outcome, although the low number of cases for some pathogens warrants further investigation. However, advanced age was associated with treatment failure, potentially due to delayed diagnosis as FIP is considered to be less common in older individuals, or to age-related changes in immune function. In summary, viral coinfections, particularly with FCV, were common and should be considered in the clinical and hygienic management of cats with FIP. Full article
(This article belongs to the Section Animal Viruses)
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14 pages, 1330 KB  
Article
The First CRISPR-Based Therapeutic (SL_1.52) for African Swine Fever Is Effective in Swine
by Naveen Verma, Alison O’Mahony, Roky Mohammad, Dylan Keiser, Craig W. Mosman, Deric Holden, Kristin Starr, Jared Bauer, Bradley Bauer, Roypim Suntisukwattana, Waranya Atthaapa, Angkana Tantituvanont, Dachrit Nilubol and Douglas P. Gladue
Viruses 2025, 17(11), 1504; https://doi.org/10.3390/v17111504 - 14 Nov 2025
Viewed by 886
Abstract
African swine fever virus (ASFV) is a high-consequence pathogen that causes African swine fever (ASF), for which mortality rates can reach 90–100%, with death typically occurring within 14 days. ASF is currently a highly contagious pandemic disease responsible for extensive losses in pig [...] Read more.
African swine fever virus (ASFV) is a high-consequence pathogen that causes African swine fever (ASF), for which mortality rates can reach 90–100%, with death typically occurring within 14 days. ASF is currently a highly contagious pandemic disease responsible for extensive losses in pig production in multiple affected countries suffering from extended outbreaks. While a limited number of vaccines to prevent ASF are in use in south-east Asia, vaccines are not widely available, are only effective against highly homologous strains of ASFV, and must be used prior to an outbreak on a farm. Currently, there is no treatment for ASF and culling affected farms is the only response to outbreaks on farms to try and prevent spreading. CRISPR/Cas systems evolved as an adaptive immune response in bacteria and archaea that function by cleaving and disrupting the genomes of invading bacteriophage pathogens. CRISPR technology has since been leveraged into an array of endonuclease-based systems used for nucleic acid detection, targeting, genomic cleavage, and gene editing, making them particularly well-suited for development as sequence-specific therapeutic modalities. The programmability of CRISPR-based therapeutics offers a compelling new way to rapidly and specifically target pathogenic viral genomes simply by using different targeting guide RNAs (gRNA) as an adaptable antiviral modality. Here, we demonstrate for the first time a specific CRISPR/Cas9 multiplexed gRNA system that targets the African swine fever viral genome, resulting in sequence-specific cleavage, leading to the reduction in the viral load in infected animals, and subsequent recovery from an otherwise lethal dose of ASFV. Moreover, animals that recovered had protective immunity to subsequent homologous ASFV infection. Full article
(This article belongs to the Special Issue Viral Diseases of Livestock and Diagnostics, 2nd Edition)
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19 pages, 1284 KB  
Article
Exploring Genomic Variations and Phenotypic Traits of Chrysodeixis includens Nucleopolyhedrovirus Isolates to Improve Soybean Pest Control
by Lucas A. Andrade, Daniel R. Sosa-Gómez, William Sihler, Bergmann M. Ribeiro, Marlinda L. Souza, Rogerio B. Lopes and Daniel M. P. Ardisson-Araújo
Viruses 2025, 17(11), 1503; https://doi.org/10.3390/v17111503 - 14 Nov 2025
Viewed by 467
Abstract
Soybean production is a cornerstone of Brazilian agriculture but is heavily threatened by insect pests such as the soybean looper Chrysodeixis includens, capable of reducing yields by up to 70% if uncontrolled. Reliance on chemical insecticides is increasingly unsustainable due to environmental [...] Read more.
Soybean production is a cornerstone of Brazilian agriculture but is heavily threatened by insect pests such as the soybean looper Chrysodeixis includens, capable of reducing yields by up to 70% if uncontrolled. Reliance on chemical insecticides is increasingly unsustainable due to environmental impacts and resistance, highlighting the need for eco-friendly alternatives. The alphabaculovirus Chrysodeixis includens nucleopolyhedrovirus (ChinNPV) is an important biocontrol agent largely used in Brazilian fields because of its host specificity and safety, although its persistence is limited by ultraviolet (UV) sensitivity. Here, we characterize two ChinNPV isolates, CNPSo-168 (C168) and Tabatinga (Tb), using genomic and phenotypic analyses. Whole-genome sequencing revealed circular dsDNA genomes of 139,290 bp (154 ORFs) for C168 and 139,131 bp (153 ORFs) for Tb, both encoding the 38 baculovirus core genes and sharing >98.9% identity with reference genomes. Comparative genomics identified 431 SNPs, including 132 nonsynonymous changes in structural, regulatory, and infection-related genes. At low concentrations, C168 showed an approximately 2-fold lower LC50 than Tb (higher potency), while both achieved near-complete mortality within 8 days at higher concentrations. This greater potency at lower concentrations reinforces the efficacy-based rationale for selecting isolate C168 for biocontrol applications. Infection reduced larval growth, pupation, and adult emergence, often with developmental impairments. Despite genetic differences, both isolates were highly UV-sensitive, and formulation tests indicated that titanium dioxide combined with kaolin conferred partial protection. These results provide insights into ChinNPV diversity and support its development as a sustainable tool for soybean pest management. Full article
(This article belongs to the Special Issue Insect Viruses and Pest Management, the Third Edition)
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11 pages, 1092 KB  
Article
ZPR1 Is Dispensable for HPV R-Loop Resolution but Regulates Host R-Loop Dynamics
by Rylann Moffitt, Steven Brooks, Elliot J. Androphy and Marsha DeSmet
Viruses 2025, 17(11), 1502; https://doi.org/10.3390/v17111502 - 13 Nov 2025
Viewed by 421
Abstract
The human papillomavirus (HPV) is a small, non-enveloped virus with a circular double-stranded DNA genome. The HPV genome encodes the E2 activator protein, which is required for viral transcription. R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals [...] Read more.
The human papillomavirus (HPV) is a small, non-enveloped virus with a circular double-stranded DNA genome. The HPV genome encodes the E2 activator protein, which is required for viral transcription. R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals to duplex DNA. These structures form during papillomavirus transcription. We and others have demonstrated that resolution of viral R loops is crucial for HPV episomal maintenance. ZPR1 is a zinc finger protein that can recruit SETX to mammalian R-loops to mediate resolution. E2 binds to and recruits SETX, an R-loop helicase, to the viral promoter. We observed E2 in complex with SETX and ZPR1. However, we found that ZPR1 depletion decreased viral R-loops while enhancing cellular R-loops. ZPR1 depletion also increased SETX binding to the viral promoter. These data suggest that ZPR1 is not required for HPV R-loop resolution, in contrast to what has been observed in mammalian cells. We detected the E2 protein associated with R-loops and found that E2 overexpression increases cell-derived R-loop formation. Analysis of TCGA datasets revealed that ZPR1, but not SETX, mRNA expression is significantly reduced in HPV-positive cervical and head and neck cancers. Together, these findings indicate that while E2 mediates HPV R-loop resolution, it also promotes R-loop accumulation in the host genome, likely through SETX sequestration. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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24 pages, 10582 KB  
Article
Characterization of Five Lytic Bacteriophages as New Members of the Genus Mosigvirus, Infecting Multidrug-Resistant Shiga Toxin-Producing Escherichia coli and Their Antibiofilm Activity
by Jong Beom Na, Seungki Lee, Eun Jeong Park, Soojin Lim, Keeman Lee, Ye Bin Kim, Tae Seon Cha, Seon Young Park and Ji Hyung Kim
Viruses 2025, 17(11), 1501; https://doi.org/10.3390/v17111501 - 13 Nov 2025
Viewed by 440
Abstract
The emergence of multidrug-resistant Shiga toxin-producing Escherichia coli (STEC) poses a major challenge to public health and necessitates the development of alternative antimicrobial strategies. This study aimed to isolate and characterize five lytic bacteriophages belonging to the genus Mosigvirus and evaluate their potential [...] Read more.
The emergence of multidrug-resistant Shiga toxin-producing Escherichia coli (STEC) poses a major challenge to public health and necessitates the development of alternative antimicrobial strategies. This study aimed to isolate and characterize five lytic bacteriophages belonging to the genus Mosigvirus and evaluate their potential as biocontrol against MDR STEC strains and their biofilms. The five bacteriophages, designated vB_EcoM-pJBB (ΦB), vB_EcoM-pJBC (ΦC), vB_EcoM-pJBJ (ΦJ), vB_EcoM-pJBK (ΦK), and vB_EcoM-pJBL (ΦL), were isolated from sewage treatment plant samples using STEC ATCC 43895 as host. Biological characterization included host range determination against 19 MDR STEC strains, one-step growth analysis, environmental stability assays, bacteriolytic activity assessment, and antibiofilm efficacy testing. Whole-genome sequencing and phylogenetic analyses were performed to determine genomic features and taxonomic classification. The phages demonstrated varying infectious capacities, lysing between six and 12 strains, with ΦL exhibiting the broadest spectrum of activity. All phages showed MOI-independent antibiofilm activity, preventing biofilm formation by approximately 70% and disrupting pre-formed biofilms by up to 80.3%. Genomic analysis revealed the absence of lysogeny markers, virulence factors, and antimicrobial resistance genes, while identifying putative depolymerase genes associated with tail fiber proteins. Phylogenetic analysis confirmed the taxonomic position of these phages within the Mosigvirus genus in the Straboviridae family. Our findings indicate that the newly identified Mosigvirus phages are promising candidates for phage-based biocontrol applications. Full article
(This article belongs to the Special Issue Bacteriophages and Biofilms 2026)
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14 pages, 1811 KB  
Article
Human Herpes Virus-8 Oral Shedding Heterogeneity Is Due to Varying Rates of Reactivation from Latency and Immune Containment
by David A. Swan, Elizabeth M. Krantz, Catherine M. Byrne, Fred Okuku, Janet Nankoma, Innocent Mutyaba, Warren Phipps and Joshua T. Schiffer
Viruses 2025, 17(11), 1500; https://doi.org/10.3390/v17111500 - 13 Nov 2025
Viewed by 450
Abstract
Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral [...] Read more.
Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission. The mechanistic drivers of different HHV-8 shedding patterns in infected individuals are unknown. We applied stochastic mathematical models to a longitudinal study of HHV-8 oral shedding in 295 individuals in Uganda who were monitored daily with oral swabs. Participants were divided into four groups based on whether they were HIV-negative or -positive, as well as KS-negative or -positive. In all groups, we observed a wide variance of shedding patterns, including no shedding, brief episodic low viral load shedding, prolonged episodic medium viral load shedding, and persistent high viral load shedding. Our model closely replicates patterns in individual data and attributes higher shedding rates to increased rates of viral reactivation and lower median viral load values to more rapid and effective engagement of cytolytic immune responses. Our model provides a framework for understanding different shedding patterns observed in individuals with HHV-8 infection. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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11 pages, 1599 KB  
Article
Biya River Virus, a Novel Hantavirus of the Eurasian Water Shrew (Neomys fodiens) in Russia
by Liudmila N. Yashina, Sergey A. Abramov, Ekaterina M. Luchnikova, Natalia A. Smetannikova, Tatiana V. Tregubchak, Tamara A. Dupal, Anton V. Krivopalov, Evgenia D. Vdovina and Richard Yanagihara
Viruses 2025, 17(11), 1499; https://doi.org/10.3390/v17111499 - 12 Nov 2025
Viewed by 469
Abstract
Hantaviridae (order Bunyavirales) is a family of negative-sense, single-stranded RNA viruses. To date, several genetically distinct hantaviruses have been found in the same species of shrews and moles. In this report, we describe Biya River virus (BIRV), a novel hantavirus detected in [...] Read more.
Hantaviridae (order Bunyavirales) is a family of negative-sense, single-stranded RNA viruses. To date, several genetically distinct hantaviruses have been found in the same species of shrews and moles. In this report, we describe Biya River virus (BIRV), a novel hantavirus detected in the Eurasian water shrew (Neomys fodiens), the principal host of Boginia virus (BOGV). Genetic analysis of the complete L- and M-genomic segments and partial S-genomic segments showed that BIRV shared a common evolutionary origin with shrew-borne Altai (ALTV) and Lena (LENV) viruses, belonging to the Mobatvirus genus, and that BIRV was distantly related to BOGV and other shrew- and mole-borne orthohantaviruses. Ancient cross-species transmission of hantaviruses, with subsequent diversification within the Soricinae subfamily in Eurasia, might have shaped the evolutionary history of BIRV, ALTV, and LENV. Full article
(This article belongs to the Section General Virology)
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14 pages, 1851 KB  
Article
Atomic Force Microscopy of Poliovirus Particles After Inactivation by Chemical Methods and Accelerated Electrons
by Sergey V. Kraevsky, Sergey L. Kanashenko, Alena V. Kolesnichenko, Yury Yu. Ivin, Anastasiia N. Piniaeva, Anastasiya A. Kovpak, Aydar A. Ishmukhametov, Sergey V. Budnik, Roman S. Churyukin, Oleg A. Shilov and Dmitry D. Zhdanov
Viruses 2025, 17(11), 1498; https://doi.org/10.3390/v17111498 - 12 Nov 2025
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Abstract
The traditional method used in the production of inactivated vaccines is chemical inactivation using beta-propiolactone or formaldehyde. An alternative method is inactivation by irradiation. Virus inactivation is often accompanied by a change in particle shape, which can negatively affect the preservation of antigens [...] Read more.
The traditional method used in the production of inactivated vaccines is chemical inactivation using beta-propiolactone or formaldehyde. An alternative method is inactivation by irradiation. Virus inactivation is often accompanied by a change in particle shape, which can negatively affect the preservation of antigens and immunogenicity. Therefore, determining the shape and structure of the viral particle after inactivation is an important step in the development of antiviral vaccines. The poliovirus strain Sabin 2 was inactivated with a dose of 30.5 ± 0.5 kGy. in a pulsed linear electron accelerator with a power of 15 kW and electron energy of 10 MeV. Samples inactivated with beta-propiolactone or formaldehyde were used for comparison. All types of inactivation resulted in D-antigen recovery as determined by enzyme-linked immunosorbent assay. There was no statistical difference between D-antigen recovery in irradiated samples and those inactivated chemically. The shape and structure of the inactivated poliovirus particles were studied using atomic force and electron microscopy. After inactivation with beta-propiolactone or formaldehyde, a change in the native icosahedral shape was observed, with many particles appearing flattened. Specific sorption of antibodies showed that the antigen is mainly preserved in intact capsids for all type of inactivation. However, in the case of inactivation with formaldehyde and accelerated electrons, a significant number of fragments measuring 10–20 nm in height were present. Their proportion was 38 ± 2% and 17 ± 2% for inactivation with accelerated electrons and formaldehyde, respectively. The proportion of bound fragments during inactivation with beta-propiolactone was less than 1%. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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13 pages, 1639 KB  
Article
Codon Usage Bias Analysis of Citrus Leaf Blotch Virus
by Xin Ren, Lifang Xu, Yuqian Yan, Ying Wang and Aijun Huang
Viruses 2025, 17(11), 1497; https://doi.org/10.3390/v17111497 - 12 Nov 2025
Viewed by 399
Abstract
Citrus leaf blotch virus (CLBV) is a positive-sense single-stranded RNA virus belonging to the genus Citrivirus within the family Betaflexiviridae. It infects a broad range of economically significant fruit crops, including citrus, kiwifruit, and apple. Surveys conducted in the field have documented [...] Read more.
Citrus leaf blotch virus (CLBV) is a positive-sense single-stranded RNA virus belonging to the genus Citrivirus within the family Betaflexiviridae. It infects a broad range of economically significant fruit crops, including citrus, kiwifruit, and apple. Surveys conducted in the field have documented appreciable incidence rates in several hosts, thereby emphasizing its emerging threat to global pomiculture. Comprehensive surveillance of CLBV genetic diversity is indispensable for predicting strain-specific epidemics and designing durable, broadly protective control strategies. Current surveys of CLBV diversity are still gene-fragment-centric, with whole-genome resolution remaining largely untapped. In this study, an analysis of codon usage bias analysis was performed using all available CLBV full-length genomes. The findings revealed that CLBV exhibits low codon usage bias, with natural selection, rather than mutational drift, being the primary driver. Phylogenetic analysis has been demonstrated to categorize isolates according to their host of origin rather than their geographical location. This observation suggests that host adaptation may supersede spatial structure in CLBV evolution and reinforce natural selection as the dominant force shaping its codon usage landscape. From the perspective of the codon adaptation index, Prunus avium is the host that exerts the greatest influence on the formation of its codon usage bias. The present study provides the first genome-wide portrait of CLBV codon usage bias, offering a robust framework for future investigations into its origin and evolutionary dynamics. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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24 pages, 3593 KB  
Article
Small Molecule Compounds Inhibit Varicella-Zoster Virus Replication by Targeting the Portal Protein–Capsid Interface
by Julius Svensmark, Emily Polk, Ellyn Kornfeind, Whitney Lane, Melissa A. Visalli and Robert J. Visalli
Viruses 2025, 17(11), 1496; https://doi.org/10.3390/v17111496 - 12 Nov 2025
Viewed by 434
Abstract
The Varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87 kDa monomer that oligomerizes to form the pORF54 portal dodecamer. Located at a single viral capsid vertex, the portal facilitates the translocation of the newly synthesized viral genome into the [...] Read more.
The Varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87 kDa monomer that oligomerizes to form the pORF54 portal dodecamer. Located at a single viral capsid vertex, the portal facilitates the translocation of the newly synthesized viral genome into the preformed empty capsid. Previously described α-methylbenzyl thiourea compounds were shown to inhibit VZV DNA encapsidation, likely by targeting pORF54. In this study, drug resistant isolates were obtained via passage of VZV in increasing concentrations of one analog, Compound I (Comp I). Mutations identified in four compound resistant isolates (amino acids 48, 304, 324 and 407) all localized to a region of the portal that was predicted to interface with capsid proteins. The portal is known to undergo significant conformational changes at the portal–capsid interface during DNA encapsidation. A set of recombinant viruses was designed to reveal the chemical and physical importance of each of the resistance mutations at the portal–capsid interface, the proposed binding site of the compound series. In addition, we employed a novel complementing cell line to show that despite the presence of the portal in the virion, DNA encapsidation did not occur. We propose that a-methylbenzyl thiourea compounds perturb interactions at or near the portal–capsid interface and prevent conformational changes needed to support DNA encapsidation. Full article
(This article belongs to the Special Issue Advances in Small-Molecule Viral Inhibitors)
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15 pages, 231 KB  
Article
Different HLA Alleles Frequencies and Their Association with Clinical Phenotypes of Acute Respiratory Infections in Children
by Natalia V. Palyanova, Olesia V. Ohlopkova, Alexey D. Moshkin, Kristina A. Stolbunova, Marina A. Stepanyuk, Ivan A. Sobolev, Olga G. Kurskaya and Alexander M. Shestopalov
Viruses 2025, 17(11), 1495; https://doi.org/10.3390/v17111495 - 12 Nov 2025
Viewed by 399
Abstract
The histocompatibility gene complex plays a vital role in the body’s immune response to infections. In this work, we analyzed clinical data for 195 children hospitalized with signs of ARI in Siberia and performed genetic analysis for them. Genotyping was performed by high-throughput [...] Read more.
The histocompatibility gene complex plays a vital role in the body’s immune response to infections. In this work, we analyzed clinical data for 195 children hospitalized with signs of ARI in Siberia and performed genetic analysis for them. Genotyping was performed by high-throughput sequencing (NGS) using the HLA-Expert kit on the MiSeq Illumina platform. The frequencies of HLA allelic variants were calculated for each variant. For the variants detected in 20 patients or more, odds ratios (OR) were calculated for two pairs of conditions: severe/non-severe course of ARI and hypoxia/no hypoxia on admission. Six allelic variants were identified for which the odds ratio showed a significant (p < 0.05) association with one of the conditions. Allele HLA-A*11:01:01G is associated (OR = 5.654, 95% CI 1.631–19.600) with severe ARVI, which is consistent with the literature data, and HLA-A*03:01:01G allele is associated with ARVI without hypoxia in children (OR = 0.317, 95% CI 0.110–0.914). Alleles HLA-B*51:01:01G (OR = 4.457, 95% CI 1.355–14.663) and HLA-C*01:02:01G (OR = 4.743, 95% CI 1.538–14.629) are associated with severe ARI. HLA-DPB1*04:02:01G (OR = 0.462, 95% CI 0.244–0.876) is associated with ARI without hypoxia and HLA-DQA1*01:02:01G (OR = 1.811, 95% CI 1.003–3.268) is associated with ARI with hypoxia. Full article
(This article belongs to the Special Issue Viral Genetic Variability and Its Role in Assessing Infectious Diseases)
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