Viruses

20 pages, 4409 KB

Open AccessArticle

Cross-Species Transmission Risks of a Quail-Origin H7N9 Influenza Virus from China Between Avian and Mammalian Hosts

by Cheng Zhang, Yifei Jin, Huan Cui, Zhongyi Wang, Zhaoliang Chen, Lei Zhang, Sihui Song, Bing Lu and Zhendong Guo

Viruses 2025, 17(10), 1402; https://doi.org/10.3390/v17101402 - 21 Oct 2025

Viewed by 290

Abstract

The H7N9 influenza viruses, which are capable of causing severe respiratory syndrome in humans, were first discovered to infect humans in 2013 and continue to pose a persistent public health threat. Quail has been proposed as a potential intermediate host that may facilitate [...] Read more.

The H7N9 influenza viruses, which are capable of causing severe respiratory syndrome in humans, were first discovered to infect humans in 2013 and continue to pose a persistent public health threat. Quail has been proposed as a potential intermediate host that may facilitate the emergence of novel reassorted influenza A viruses with the capacity to infect humans across species barriers; however, information on the biological characterization of quail H7N9 remains limited. In this study, we isolated and identified an avian H7N9 influenza virus from quails, designated as A/quail/Hebei/CH06-07/2018 (H7N9) and abbreviated as CH06-07, in Hebei, China. Phylogenetic analyses revealed that both the HA gene and the NA gene of CH06-07 were clustered in the Eurasian lineage. Furthermore, CH06-07 exhibited binding affinity for both α2,3-linked and α2,6-linked sialic acid receptors and demonstrated high pathogenicity in both quails and mice. Notably, transmission studies revealed that CH06-07 not only exhibited efficient inter-quail transmission and inter-guinea pig transmission but also demonstrated effective cross-species transmission. Importantly, infected quails and guinea pigs generated significant quantities of viral aerosols (≥18,998 ± 1672 copies per liter of air at 3 days post-infection), and infectious viruses were successfully recovered from environmental aerosols. These findings highlight the necessity for continuous surveillance of the prevalence of quail-origin H7N9 influenza A viruses in poultry populations due to their potential threat to human health. Full article

(This article belongs to the Section Animal Viruses)

► Show Figures

Figure 1

6 pages, 191 KB

Open AccessEditorial

Viruses Beyond Pathogens: Partners and Tools for Biotechnology

by Patrick Materatski and Carla Varanda

Viruses 2025, 17(10), 1401; https://doi.org/10.3390/v17101401 - 21 Oct 2025

Viewed by 263

Abstract

For many years, viruses were regarded solely as agents of devastating diseases in humans, animals, and plants [...] Full article

(This article belongs to the Special Issue The Application of Viruses to Biotechnology 3.0)

21 pages, 305 KB

Open AccessArticle

Baseline Dysregulation in B, T, and NK Cells in COVID-19 Predicts Increased Late Mortality but Not Long-COVID Symptoms: Results from a Single-Center Observational Study

by Aleksandra Matyja-Bednarczyk, Radosław Dziedzic, Anna Drynda, Ada Gradzikiewicz, Monika Bociąga-Jasik, Krzysztof Wójcik, Sabina Lichołai, Karolina Górka, Natalia Celejewska-Wójcik, Tomasz Stachura, Kamil Polok, Lech Zaręba, Teresa Iwaniec, Krzysztof Sładek and Stanisława Bazan-Socha

Viruses 2025, 17(10), 1400; https://doi.org/10.3390/v17101400 - 21 Oct 2025

Viewed by 4136

Abstract

The SARS-CoV-2 pandemic presents a broad clinical spectrum from asymptomatic cases to severe respiratory failure with high mortality. Severe COVID-19 is characterized by immune dysregulation, including lymphopenia and alterations in the counts of T, B, and NK cells in peripheral blood. Due to [...] Read more.

The SARS-CoV-2 pandemic presents a broad clinical spectrum from asymptomatic cases to severe respiratory failure with high mortality. Severe COVID-19 is characterized by immune dysregulation, including lymphopenia and alterations in the counts of T, B, and NK cells in peripheral blood. Due to the limited data on long-term outcomes related to immune dysregulation, we aimed to analyze immunologic features at baseline in severe and mild COVID-19 cases and assess follow-up characteristics associated with later mortality and long-COVID signs. We included adult patients consecutively hospitalized with COVID-19 between June and November 2020 at the University Hospital in Kraków, corresponding to the first and second waves of COVID-19 in Poland. We enrolled only those who had been thoroughly assessed in terms of clinic and laboratory data, including immunological workups, and survived the acute phase of the disease. In 2025, between February and April (median time of follow-up: 54 months), we conducted a telephone questionnaire on long-COVID symptoms among survivors who had given their consent. Statistical analyses were performed to compare groups with severe and mild disease in terms of dysregulation in lymphocyte subpopulations and the follow-up outcomes. The study included 103 COVID-19 patients, comprising 53 severe (based on the need for at least high-flow nasal oxygen therapy) and 50 mild cases, with no differences in age, sex, and body mass index. Severe COVID-19 patients compared to mild cases had lower CD3+ T cells (count and percentage), CD4+ T cells (count and percentage), CD8+ T cells (count), and NK cells (count), but higher CD19+ B cells (percentage) at baseline (p < 0.05, all). At the time of follow-up, we evaluated 80 patients (77.7% of the baseline participants), with 23 (22.3%) patients lost to follow-up. Among patients analyzed in the follow-up, 23 (28.8%) had died, and 29 of the 57 survivors (50.9%) reported persistent long-COVID symptoms. Patients who died had significantly lower baseline counts of CD3+ T cells (377 vs. 655 cells/µL), CD4+ T cells (224 vs. 372 cells/µL), CD8+ T cells (113 vs. 188 cells/µL), and NK cells (118 vs. 157 cells/µL) compared to survivors (p < 0.05, all). Notably, the percentage of CD19+ B cells was higher in deceased individuals (19.2% vs. 13.5%; p = 0.049). In contrast, we did not document differences in baseline immunological data among survivors with and without long-COVID signs. Our study suggests that dysregulation in lymphocyte subpopulations during the COVID-19 acute phase may be associated with increased late mortality, but not with the persistence of long-COVID symptoms. Full article

(This article belongs to the Special Issue COVID-19 Complications and Co-infections)

17 pages, 5623 KB

Open AccessArticle

JC Virus Agnogene Regulates Histone-Modifying Enzymes via PML-NBs: Transcriptomics in VLP-Expressing Cells

by Yukiko Shishido-Hara and Takeshi Yaoi

Viruses 2025, 17(10), 1399; https://doi.org/10.3390/v17101399 - 21 Oct 2025

Viewed by 274

Abstract

JC virus (JCV) replicates within the nuclei of glial cells in the human brain and causes progressive multifocal leukoencephalopathy. JCV possesses a small, circular, double-stranded DNA genome, divided into early and late protein-coding regions. The non-coding control region (NCCR) functions bidirectionally for both [...] Read more.

JC virus (JCV) replicates within the nuclei of glial cells in the human brain and causes progressive multifocal leukoencephalopathy. JCV possesses a small, circular, double-stranded DNA genome, divided into early and late protein-coding regions. The non-coding control region (NCCR) functions bidirectionally for both early and late genes, and the agnogene is located downstream of TCR and upstream of three capsid proteins in the late region. Previously, in cell culture systems, we demonstrated that these capsid proteins accumulate in intranuclear domains known as promyelocytic leukemia nuclear bodies (PML-NBs), where they assemble into virus-like particles (VLPs). To investigate the agnogene’s function, VLPs were formed in its presence or absence, and differential gene expression was analyzed using microarray technology. The results revealed altered expression of histone-modifying enzymes, including methyltransferases (EHMT1, PRMT7) and demethylases (KDM2B, KDM5C, KDM6B), as well as various kinases and phosphatases. Notably, CTDP1, which dephosphorylates the C-terminal domain of an RNA polymerase II subunit, was also differentially expressed. The changes were predominant in the presence of the agnogene. These findings indicate that the agnogene and/or its protein product likely influence epigenetic regulation associated with PML-NBs, which may influence cell cycle control. Consistently, in human brain tissue, JCV-infected glial cells displayed maintenance of a diploid chromosomal complement, likely through G2 arrest. The precise mechanism of this, however, remains to be elucidated. Full article

(This article belongs to the Special Issue JC Polyomavirus)

► Show Figures

Figure 1

24 pages, 1691 KB

Open AccessReview

Immune Evasion by the NSs Protein of Rift Valley Fever Virus: A Viral Houdini Act

by Kaylee Petraccione, James G. Omichinski and Kylene Kehn-Hall

Viruses 2025, 17(10), 1398; https://doi.org/10.3390/v17101398 - 21 Oct 2025

Viewed by 478

Abstract

Rift Valley fever virus (RVFV) is a negative-sense arbovirus that causes several severe diseases, including hemorrhagic fever in ruminants and humans. There are currently no FDA-approved vaccines or therapeutics for RVFV. The viral nonstructural protein NSs acts like a molecular Harry Houdini, the [...] Read more.

Rift Valley fever virus (RVFV) is a negative-sense arbovirus that causes several severe diseases, including hemorrhagic fever in ruminants and humans. There are currently no FDA-approved vaccines or therapeutics for RVFV. The viral nonstructural protein NSs acts like a molecular Harry Houdini, the world-famous escape artist, to help the virus evade the host’s innate immune response and serves as the main virulence factor of RVFV. In this review, we discuss the molecular mechanisms by which NSs interacts with multiple factors to modulate host processes, evade the host immune response, and facilitate viral replication. The impact of NSs mutations that cause viral attenuation is also discussed. Understanding the molecular mechanisms by which NSs evades the host innate immune response is crucial for developing novel therapeutics and vaccines targeting RVFV. Full article

(This article belongs to the Special Issue Bunyaviruses 2025)

► Show Figures

Figure 1

14 pages, 1252 KB

Open AccessArticle

Metatranscriptomic Analysis of Oropharyngeal Samples Reveals Common Respiratory Viruses and a Potential Interspecies Transmitted Picobirnavirus in the Wayuu Population, La Guajira, Colombia

by Beatriz Elena De arco-Rodríguez, Jhindy Tatiana Pérez-Lozada, Katherine Laiton-Donato, Dioselina Peláez-Carvajal, Gloria Mercedes Puerto-Castro and Diego Alejandro Álvarez-Díaz

Viruses 2025, 17(10), 1397; https://doi.org/10.3390/v17101397 - 21 Oct 2025

Viewed by 494

Abstract

Acute respiratory infections and other infectious diseases causing acute febrile syndrome are major public health concerns in Colombia, particularly among vulnerable populations such as the Wayuu Indigenous community in Manaure, La Guajira. To investigate their viral etiology, 55 nasopharyngeal swabs and 58 serum [...] Read more.

Acute respiratory infections and other infectious diseases causing acute febrile syndrome are major public health concerns in Colombia, particularly among vulnerable populations such as the Wayuu Indigenous community in Manaure, La Guajira. To investigate their viral etiology, 55 nasopharyngeal swabs and 58 serum samples were collected from febrile Wayuu individuals in Manaure. RT-qPCR screening identified Coronavirus, Enteroviruses, Adenovirus, and Influenza A/B in respiratory samples, while no arboviruses were detected in serum. Sixteen representative samples underwent metatranscriptomic next-generation sequencing (mtNGS) using the Chan-Zuckerberg ID (CZ-ID) platform. This analysis confirmed RT-qPCR findings and additionally revealed six viral contigs related to Orthopicobirnavirus hominis. Sequencing coverage enabled the reconstruction of a consensus RdRp segment, which was phylogenetically compared with sequences from diverse hosts. The virus clustered within genogroup 1, alongside Colombian isolates linked to severe acute respiratory infection. The absence of strict host-specific clustering suggests possible interspecies transmission. These findings underscore the complementary roles of targeted and unbiased approaches: RT-qPCR detected common respiratory viruses, whereas mtNGS uncovered a virus previously unreported in this community. Overall, mtNGS emerges as a powerful tool to support viral surveillance and provide baseline evidence in indigenous populations, emphasizing the need to decentralize advanced molecular diagnostics and strengthen public health capacity in Colombia. Full article

(This article belongs to the Special Issue Virus Biosensing)

► Show Figures

Graphical abstract

2 pages, 150 KB

Open AccessCorrection

Correction: Shehata et al. The Hidden Threat: Rodent-Borne Viruses and Their Impact on Public Health. Viruses 2025, 17, 809

by Awad A. Shehata, Rokshana Parvin, Shadia Tasnim, Phelipe Magalhães Duarte, Alfonso J. Rodriguez-Morales and Shereen Basiouni

Viruses 2025, 17(10), 1396; https://doi.org/10.3390/v17101396 - 21 Oct 2025

Viewed by 193

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2026)

30 pages, 3776 KB

Open AccessSystematic Review

Vertical Transmission of Hepatitis B and C—Then and Now—A Comprehensive Literature Systematic Review

by Ruxandra Dobritoiu, Daniela Pacurar, Raluca Maria Vlad and Doina Anca Plesca

Viruses 2025, 17(10), 1395; https://doi.org/10.3390/v17101395 - 20 Oct 2025

Viewed by 543

Abstract

Background: According to a WHO global hepatitis report, the global prevalence of hepatitis B in 2022 was 254 million and for hepatitis C it was 50 million. The estimated number of people newly infected by viral hepatitis declined from 3 million in 2019 [...] Read more.

Background: According to a WHO global hepatitis report, the global prevalence of hepatitis B in 2022 was 254 million and for hepatitis C it was 50 million. The estimated number of people newly infected by viral hepatitis declined from 3 million in 2019 to 2.2 million in 2022. Of these, 1.2 million are hepatitis B infections and nearly 1.0 million are hepatitis C infections. Regarding vertical transmission, it is estimated that 4 to 5 million children are infected worldwide every year from HBV-positive mothers. The United States declared that hepatitis C is the commonest chronic blood-borne infection, with an increase in HCV birth infections from 1.8 to 4.7 per 1000 births. Objectives: This systematic review focuses on highlighting the most suitable screening methods and maternal interventions to prevent HBV/HCV mother-to-child transmission, as well as the appropriate prophylactic strategies for newborns. Materials and methods: We searched a medical database (PubMed) to find papers regarding mother-to-child transmission of hepatitis B and C. Inclusion criteria were human-based studies, studies with large cohorts of subjects, studies conducted in different parts of the globe and position papers from various international associations. Exclusion criteria were non-human-based studies and non-English publications. To present and synthesize results we made use of thematic analysis and narrative synthesis. Results: We included 103 publications. For hepatitis B, the combination of maternal antiviral therapy during pregnancy and timely administration of HBV vaccine alongside HBIG to the newborn has proven to be highly effective in lowering transmission rates. Hepatitis C vertical transmission lacks an effective vaccine or immuno-prophylaxis, turning prevention strategies into a continuous battle. Conclusions: Vertical transmission of hepatitis B and C continues to be a major contributor to the global burden of chronic viral hepatitis. Strengthening prenatal care programs, improving access to diagnostic and therapeutic resources and enhancing public health policies are essential to curb vertical transmission of both hepatitis B and C. Full article

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

► Show Figures

Figure 1

20 pages, 3601 KB

Open AccessArticle

Investigating Apple Rubbery Wood Virus 2: HTS-Based Detection in Hungary and Involvement of sRNA-Based Regulation Processes During Its Infection

by Almash Jahan and Éva Várallyay

Viruses 2025, 17(10), 1394; https://doi.org/10.3390/v17101394 - 20 Oct 2025

Viewed by 270

Abstract

Pomme fruits are propagated vegetatively, thereby facilitating frequent viral transmission. The causative agent of apple rubbery wood disease, apple rubbery wood virus 2 (ARWV2), can infect apple and pear. The branches of ARWV2-infected, symptomatic trees are flexible due to the decreased lignification of [...] Read more.

Pomme fruits are propagated vegetatively, thereby facilitating frequent viral transmission. The causative agent of apple rubbery wood disease, apple rubbery wood virus 2 (ARWV2), can infect apple and pear. The branches of ARWV2-infected, symptomatic trees are flexible due to the decreased lignification of the xylem. In this research, we reanalysed our small RNA (sRNA) HTS datasets to survey the presence of ARWV2 in Hungary. Validation of HTS using RT-PCR revealed infection in several cultivars. The following RT-PCR-based survey revealed the infection of 17 trees, including not only apple, but also pears, one quince, and a rootstock, without showing any rubbery wood symptoms. Analysis of the sRNA datasets allowed us to profile the sRNA pattern of ARWV2-infected and non-infected trees, and characterise the differential expression pattern of vsiRNAs, sRNAs, and miRNAs targeting the lignin biosynthetic pathway. The results confirmed that the gene-expression changes in the genes that regulate lignification cannot be directly correlated with the presence of the virus, which can explain its frequent latent presence. The variable titre and sequence of the virus, and mixed-infection status of the trees, make its reliable diagnostics challenging, which could be achieved as a result of further research. Full article

(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)

► Show Figures

Graphical abstract

21 pages, 3657 KB

Open AccessArticle

Reinfection Dynamics of Disease-Free Cassava Plants in Three Agroecological Regions of Côte d’Ivoire

by John Steven S. Seka, Justin S. Pita, Modeste K. Kouassi, William J. -L. Amoakon, Bekanvié S. M. Kouakou, Mariam Combala, Daniel H. Otron, Brice Sidoine Essis, Konan Evrard B. Dibi, Angela O. Eni, Nazaire K. Kouassi and Fidèle Tiendrébéogo

Viruses 2025, 17(10), 1393; https://doi.org/10.3390/v17101393 - 20 Oct 2025

Viewed by 438

Abstract

Cassava mosaic disease (CMD) is caused by begomoviruses and can result in yield losses of up to 90% in susceptible varieties. Using disease-free planting material from in vitro cultures is one of the most effective ways of controlling this disease. A CMD epidemiological [...] Read more.

Cassava mosaic disease (CMD) is caused by begomoviruses and can result in yield losses of up to 90% in susceptible varieties. Using disease-free planting material from in vitro cultures is one of the most effective ways of controlling this disease. A CMD epidemiological assessment was conducted in fields established with disease-free plantlets in Bouaké, Dabou, and Man, selected for their contrasting agroecological and CMD prevalence conditions. Virus and whitefly species characterisation was performed using PCR and sequencing. CMD incidence and severity were lowest at the Man site and highest at the Dabou site. Although whitefly abundance was relatively low at the Man and Bouaké sites compared to the Dabou site, they were a significant factor in the spread of the disease. While all resistant varieties remained asymptomatic, susceptible and tolerant varieties became infected, and some tolerant varieties were able to recover from the disease. Molecular analyses revealed the presence of two viral species: Begomovirus manihotis (ACMV) and Begomovirus manihotiscameroonense (EACMCMV). No viral infection was detected 4 weeks after planting (WAP). Cases of single infection and double infection were observed at 12 and 20 WAP. Also, no double infections were found at the Man site, in contrast to the Bouaké site (12 WAP: 2.36%) and Dabou site (12 WAP: 2.59%; 20 WAP: 5.76%). EACMCMV was found in a single infection in Bouaké (12 WAP: 1.39%) and Man (20 WAP: 0.66%). The whitefly species Bemisia tabaci and Bemisia afer were most commonly found feeding on all cassava varieties. A high diversity of whitefly species was observed in Bouaké and Dabou compared to Man. Furthermore, the Bemisia tabaci species identified in this study was found to be able to transmit ACMV and EACMCMV viruses. These highlights would contribute to improving CMD management and control strategies. Full article

(This article belongs to the Special Issue Economically Important Viruses in African Crops)

► Show Figures

Figure 1

19 pages, 1564 KB

Open AccessArticle

A Novel Municipal-Level Approach to Uncover the Hidden Burden of Hepatitis C: A Replicable Model for National Elimination Strategies

by Pietro Torre, Silvana Mirella Aliberti, Tommaso Sarcina, Mariano Festa, Chiara D’Amore, Giuseppe D’Adamo, Michele Gambardella, Antonella Santonicola, Gaetano Manzi, Mario Masarone, Mario Capunzo and Marcello Persico

Viruses 2025, 17(10), 1392; https://doi.org/10.3390/v17101392 - 19 Oct 2025

Viewed by 468

Abstract

Background: Hepatitis C Virus (HCV) remains a global health challenge as WHO elimination targets are not achievable in most countries, mainly due to the high number of undiagnosed individuals. In Italy, where national elimination efforts are ongoing, regional disparities further hinder progress. This [...] Read more.

Background: Hepatitis C Virus (HCV) remains a global health challenge as WHO elimination targets are not achievable in most countries, mainly due to the high number of undiagnosed individuals. In Italy, where national elimination efforts are ongoing, regional disparities further hinder progress. This study aimed to characterize the hidden burden of chronic HCV infection across t he territory of the Province of Salerno, Southern Italy, to suggest a novel municipal-level screening approach, with implications for national strategies. Methods: We analyzed records of residents diagnosed with chronic HCV infection and linked to care between 2015 and 2022. Data included age, sex, municipality of residence, HCV genotype, and fibrosis stage. Observed prevalence was compared with expected prevalence derived from national/regional benchmarks. Municipalities were categorized as urban or rural based on the resident population. Results: A total of 3528 cases were identified across 139 municipalities. Patients had a mean age of 63 years, and 54% were male. Half were diagnosed at an advanced stage (F3–F4), with genotype 1b being predominant. The hidden burden increased with age and showed a higher prevalence in rural areas compared to urban ones, with values of about 7 vs. 3 per 1000 inhabitants respectively. Logistic regression analysis identified age, male sex, urban residence, and genotype 1b as factors associated with advanced fibrosis or cirrhosis. Conclusions: This is the first Italian study to apply a standardized municipal-level classification to quantify the hidden burden of HCV. The model identifies underdiagnosed areas, highlights urban–rural disparities (a higher degree of underdiagnosis in rural areas versus a higher frequency of late diagnosis in urban ones), and provides a replicable tool for precision public health. Its adoption could enhance national HCV elimination efforts by supporting targeted screening, optimized resource allocation, and equitable access to care. Full article

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

► Show Figures

Figure 1

18 pages, 4515 KB

Open AccessArticle

A Highly Sensitive BRET-Based Reporter for Live-Cell Detection of HIV-1 Protease Activity and Inhibitor Screening

by Matteo Centazzo, Atalie Verra-Victoria Djossou, Silvia Pavan and Gualtiero Alvisi

Viruses 2025, 17(10), 1391; https://doi.org/10.3390/v17101391 - 19 Oct 2025

Viewed by 371

Abstract

Given their role in viral polyprotein processing, viral proteases (PRs) are excellent targets for antiviral therapy. Most assays developed for screening PR inhibitors are in vitro assays, and therefore have several limitations, including the inability to account for cell permeability, toxicity and the [...] Read more.

Given their role in viral polyprotein processing, viral proteases (PRs) are excellent targets for antiviral therapy. Most assays developed for screening PR inhibitors are in vitro assays, and therefore have several limitations, including the inability to account for cell permeability, toxicity and the need for compounds activation within cells. The development of cellular reporters overcoming these limitations is therefore highly desirable. In this study, we developed two different Bioluminescence Resonance Energy Transfer (BRET)-based reporters for Human Immunodeficiency virus-1 (HIV-1) PR, allowing the simultaneous monitoring of cell viability and HIV-1 PR activity. The reporters employ two different BRET pairs as donor and acceptor moieties: Renilla luciferase (RLuc) with Yellow Fluorescent Protein (YFP), and Nano luciferase (NLuc) with mNeonGreen (mNG), both linked by the HIV-1 p2/p7 cleavage site. While both reporters specifically detected HIV-1 protease activity, mNG-p2/p7-NLuc exhibited higher sensitivity, increased energy transfer and better spectral separation between donor and acceptor emissions, resulting in a significantly higher BRET ratio. mNG-p2/p7-NLuc was used to quantify the effect of a panel of protease inhibitors in living cells, assessing simultaneously cell viability and HIV-1 PR activity. Additionally, it was employed to measure the potency of well-known HIV-1 PR inhibitors. Together, these findings demonstrate the utility of the mNG-p2/p7-NLuc reporter as a cell-based tool for the evaluation of HIV-1 PR activity and inhibitor efficacy. Its dual-readout capability provides a valuable platform for antiviral drug screening in physiologically relevant conditions. Full article

(This article belongs to the Special Issue HIV Protease)

► Show Figures

Figure 1

13 pages, 2810 KB

Open AccessArticle

Assessment of Biological Properties of Recombinant Lumpy Skin Disease Viruses with Deletions of Immunomodulatory Genes

by Aisha Issabek, Arailym Bopi, Nurlan Kozhabergenov, Bermet Khudaibergenova, Kulyaisan Sultankulova and Olga Chervyakova

Viruses 2025, 17(10), 1390; https://doi.org/10.3390/v17101390 - 19 Oct 2025

Viewed by 293

Abstract

Rational design of capripoxvirus-based vaccine vectors can be achieved by knockout of immunomodulatory genes. In this study, the effect of knockout of the immunomodulatory genes LSDV005, LSDV008 and LSDV066 on the replication of Lumpy skin disease virus in cell cultures and the immune [...] Read more.

Rational design of capripoxvirus-based vaccine vectors can be achieved by knockout of immunomodulatory genes. In this study, the effect of knockout of the immunomodulatory genes LSDV005, LSDV008 and LSDV066 on the replication of Lumpy skin disease virus in cell cultures and the immune response to an integrated foreign antigen were assessed. The knockout of genes was performed by homologous recombination under conditions of temporary dominant selection. It was found that single knockout of the LSDV005 gene and the LSDV008 gene did not affect the replicative activity of recombinant viruses in vitro (Atyrau-5 and Atyrau-B). Both single knockout of the LSDV066 gene and in combination with knockout of LSDV005 or LSDV008 led to a decrease in the replicative activity of recombinant LSDVs. The recombinant Atyrau-5J(IL18) with LSDV005 gene knockout induced production of antibodies to the integrated antigen in mice. Prime-boost vaccination with all studied recombinants increased the level of interferon-γ. In addition, during immunization with the recombinant Atyrau-5J(IL18) secretion of interleukin-2 was significantly increased. The study of the functions of immunomodulatory genes and their effect on the expression of inserted sequences of foreign antigens is promising for the creation of highly effective polyvalent vector vaccines for animals. Full article

(This article belongs to the Special Issue Veterinary Virology: Unraveling Host–Pathogen Interactions for Animal Health)

► Show Figures

Graphical abstract

21 pages, 2634 KB

Open AccessArticle

Molecular Epidemiology of Hepatitis E Virus in Hungary (2018–2025): Emergence of Rare Subtypes and First Detection of HEV-4 in Central Europe

by Ágnes Dencs, Andrea Hettmann, Levente Zsichla, Viktor Müller, Anett Dömötör, Ágnes Barna-Lázár, Erzsébet Barcsay and Mária Takács

Viruses 2025, 17(10), 1389; https://doi.org/10.3390/v17101389 - 18 Oct 2025

Viewed by 399

Abstract

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis in Europe, with increasing recognition in immunocompromised patients. While genotype 3 (HEV-3) is most prevalent in the region, molecular epidemiology data from Hungary have been limited. HEV strains from 118 RNA-positive patients [...] Read more.

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis in Europe, with increasing recognition in immunocompromised patients. While genotype 3 (HEV-3) is most prevalent in the region, molecular epidemiology data from Hungary have been limited. HEV strains from 118 RNA-positive patients diagnosed between 2018 and 2025 were genotyped. Next-generation sequencing yielded near-complete HEV genomes for 76 samples. HEV-3 was dominant (98.3%). Subtype 3a was the most common (34.7%), followed by 3c, 3f, and 3e. Rare subtypes (3g, 3h, 3i, 3m, 3ra) and HEV-4b were detected for the first time in Hungary. Among immunocompromised patients, 41.6% developed chronic infection. Ribavirin resistance-associated mutations G1634R and V1479I were frequently detected. In silico analysis of potential multiple infections indicated the presence of at least two HEV strains of distinct origin in six patients. Our surveillance revealed extensive genetic diversity of HEV in Hungary. The detection of rare HEV-3 subtypes and the first documented occurrence of HEV-4b in the country highlight likely viral introductions linked to the increasing international trade. Ongoing surveillance is essential in protecting high-risk groups and limiting HEV transmission in a globalized food system. Full article

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

► Show Figures

Graphical abstract

11 pages, 924 KB

Open AccessCommunication

Serological Evidence of Exposure to Eurasian-Lineage HPAI H5N1 Clade 2.3.4.4b in Wild Mammals in Ohio, USA, 2024–2025

by Mohammad Jawad Jahid, Madison C. Owsiany, Lauren M. Smith, Bryant M. Foreman, Zijing Cao, Deborah L. Carter, David E. Stallknecht, Brendan Shirkey, Rebecca L. Poulson and Jacqueline M. Nolting

Viruses 2025, 17(10), 1388; https://doi.org/10.3390/v17101388 - 18 Oct 2025

Viewed by 427

Abstract

The Goose/Guandong lineage of highly pathogenic avian influenza virus [A/Goose/Guangdong/1/1996(H5N1)] is the progenitor of the currently circulating Eurasian-lineage highly pathogenic avian influenza H5N1 clade 2.3.4.4b and has been the most consequential highly pathogenic avian influenza lineage globally. Despite increased reports of infections, the [...] Read more.

The Goose/Guandong lineage of highly pathogenic avian influenza virus [A/Goose/Guangdong/1/1996(H5N1)] is the progenitor of the currently circulating Eurasian-lineage highly pathogenic avian influenza H5N1 clade 2.3.4.4b and has been the most consequential highly pathogenic avian influenza lineage globally. Despite increased reports of infections, the extent of exposure and role of wild mammals in the ecology and transmission dynamics of the virus remains poorly understood. We surveyed wild mammals in Ohio, United States to investigate the potential spillover of highly pathogenic H5N1 avian influenza clade 2.3.4.4b. While no active infections—defined as positive results indicative of viral replication and potential propagation—were detected by swab-based molecular tests, serological assays revealed antibodies against multiple avian influenza virus antigens in raccoons and opossums. Specifically, antibodies to avian influenza virus nucleoprotein were detected in 54.9% (n = 61) of samples using enzyme-linked immunosorbent assay; antibodies to Eurasian-lineage highly pathogenic avian influenza H5 clade 2.3.4.4b and North American low pathogenic avian influenza H5 were detected in 43.2% (n = 48) and 22.5% (n = 25) of samples, respectively, using virus neutralization assays; and antibodies to avian influenza virus neuraminidase were detected in 44.1% (n = 49) of samples using enzyme-linked lectin assay. All seropositive animals were sampled at Ohio marshes with previously confirmed highly pathogenic avian influenza H5N1 detections in waterfowl. These findings suggest prior exposure of wild mammals to these viruses without mortality events. Wild mammals may play an intermediary role in the mammalian adaptation of avian influenza A viruses. Therefore, ongoing surveillance of wild mammals is crucial for assessing the risk to public health. Full article

(This article belongs to the Special Issue Influenza Viruses in Wildlife 2025)

► Show Figures

Figure 1

17 pages, 2098 KB

Open AccessArticle

SARS-CoV-2 Entry Can Be Mimicked in C. elegans Expressing Human ACE2: A New Tool for Pharmacological Studies

by Margherita Romeo, Sara Baroni, Maria Monica Barzago, Samuela Gambini, Ada De Luigi, Daniela Iaconis, Andrea Rosario Beccari, Maddalena Fratelli and Luisa Diomede

Viruses 2025, 17(10), 1387; https://doi.org/10.3390/v17101387 - 18 Oct 2025

Viewed by 298

Abstract

Testing medical countermeasures for SARS-CoV-2 transmission using vertebrates can be hindered by legislation regulating animal experimentation, high costs, and ethical concerns. To overcome these challenges, we propose a new Caenorhabditis elegans strain that constitutively expresses the human angiotensin-converting enzyme 2 receptor (ACE2). This [...] Read more.

Testing medical countermeasures for SARS-CoV-2 transmission using vertebrates can be hindered by legislation regulating animal experimentation, high costs, and ethical concerns. To overcome these challenges, we propose a new Caenorhabditis elegans strain that constitutively expresses the human angiotensin-converting enzyme 2 receptor (ACE2). This resulted in significant impairment of reproduction and a defect in pharyngeal function compared to wild-type (WT) worms. SARS-CoV-2 infection was simulated by treating worms with the receptor-binding domain (RBD) of the spike protein, which caused dose-dependent and time-dependent pharyngeal impairment in ACE2 worms but not in WT worms. The toxicity of RBD was prevented by administering an anti-human ACE2 antibody, demonstrating that interactions with the ACE2 receptor are essential. The ACE2-expressing worm strain was further used for pharmacological research with Raloxifene. In vitro, 1–3 μM of Raloxifene reduced the entry of lentiviral particles carrying the Wuhan variant and B.1.1.7 UK and B.1.1.529 Omicron strains into HEK293-ACE2, in addition to particles expressing N501Y-mutated or P681H-mutated spike proteins. Raloxifene (0.1–1 μM) completely counteracted RBD toxicity in ACE2 worms, indicating that this strain offers a cost-effective in vivo screening platform for molecules with effects involving interactions with the ACE2 receptor. Full article

(This article belongs to the Section Coronaviruses)

► Show Figures

Figure 1

19 pages, 1652 KB

Open AccessReview

Metabolic Hostile Takeover: How Influenza Virus Reprograms Cellular Metabolism for Replication

by Xianfeng Hui, Xiaowei Tian, Shihuan Ding, Ge Gao, Xin Zhao, Jiyan Cui, Yiru Hou, Tiesuo Zhao and Hui Wang

Viruses 2025, 17(10), 1386; https://doi.org/10.3390/v17101386 - 17 Oct 2025

Viewed by 412

Abstract

Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including [...] Read more.

Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including enhanced glycolysis, suppression of oxidative phosphorylation, diversion of TCA cycle intermediates for biosynthesis, and upregulation of lipid and amino acid metabolism. Key nutrients like glucose, glutamine, and serine are redirected to support viral RNA synthesis, protein production, and membrane formation. Moreover, these metabolic changes also modulate host immune responses, potentially aiding in immune evasion. We highlight the role of transcription factors such as SREBPs in lipid synthesis and the impact of one-carbon metabolism on epigenetic regulation. Finally, we discuss how targeting virus-induced metabolic shifts, using agents like 2-deoxyglucose or fatty acid synthesis inhibitors, offers promising avenues for antiviral intervention, while emphasizing the need for selective approaches to minimize harm to normal cells. Full article

(This article belongs to the Special Issue Interaction Between Influenza Virus and Host Cell)

► Show Figures

Figure 1

11 pages, 957 KB

Open AccessTechnical Note

vvv2_align_SE, vvv2_align_PE/vvv2_display: Galaxy-Based Workflows and Tool Designed to Perform, Summarize and Visualize Variant Calling and Annotation in Viral Genome Assemblies

by Alexandre Flageul, Edouard Hirchaud, Céline Courtillon, Flora Carnet, Paul Brown, Béatrice Grasland and Fabrice Touzain

Viruses 2025, 17(10), 1385; https://doi.org/10.3390/v17101385 - 17 Oct 2025

Viewed by 253

Abstract

Background: Next-generation sequencing (NGS) analysis of viral samples generates results dispersed across multiple files—genome assembly, variant calling, and functional annotations—making integrated interpretation challenging. Variants often yield numerous low-frequency or non-significant variants, yet only a small fraction are biologically relevant. Virologists must manually [...] Read more.

Background: Next-generation sequencing (NGS) analysis of viral samples generates results dispersed across multiple files—genome assembly, variant calling, and functional annotations—making integrated interpretation challenging. Variants often yield numerous low-frequency or non-significant variants, yet only a small fraction are biologically relevant. Virologists must manually sift through extensive data to identify meaningful mutations, a time-consuming and error-prone process. To address these practical challenges, we developed vvv2_display, a dedicated summarization and visualization tool, integrated within comprehensive Galaxy workflows. Results: vvv2_display streamlines variant interpretation by consolidating key results into two concise and interoperable outputs. The first output is a PNG image showing alignment coverage depth and genomic annotations, with significant variants displayed along the genome as symbols whose height reflects frequency and shape indicates the affected protein. At a glance, this enables virologists to identify all deviations from a reference viral genome. Each significant variant is assigned a unique identifier that directly links to the second output: a tab-separated (TSV) text file listing only high-confidence variants, with frequencies, flanking nucleotides, and impacted genes and proteins. This cross-referenced design supports rapid, accurate, and intuitive data exploration. Availability: vvv2_display is open source, available on Github and installable via Mamba. Full article

(This article belongs to the Section Animal Viruses)

► Show Figures

Figure 1

22 pages, 6879 KB

Open AccessArticle

Dissecting the Unique Self-Assembly Landscape of the HIV-2 Capsid Protein

by Matthew Cook, Pushpanjali Bhardwaj, Faith Lozano, Christian Freniere, Ryan J. Malonis and Yong Xiong

Viruses 2025, 17(10), 1384; https://doi.org/10.3390/v17101384 - 17 Oct 2025

Viewed by 411

Abstract

Human immunodeficiency virus type 2 (HIV-2) is a lentivirus closely related to HIV-1 but exhibits distinct molecular and clinical features that influence viral infectivity and efficacy of antiretroviral therapy. The HIV capsid is a critical structural component with multifaceted roles during infection and [...] Read more.

Human immunodeficiency virus type 2 (HIV-2) is a lentivirus closely related to HIV-1 but exhibits distinct molecular and clinical features that influence viral infectivity and efficacy of antiretroviral therapy. The HIV capsid is a critical structural component with multifaceted roles during infection and mediates some of the observed divergence between HIV-1 and HIV-2. Unlike HIV-1, study of the HIV-2 capsid is limited and standard protocols for the in vitro assembly of HIV-1 capsid protein (CA) lattice structures have not been successfully translated to the HIV-2 context. This work identifies effective approaches for the assembly of the HIV-2 CA lattice and leverages this to biochemically characterize HIV-2 CA assemblies and mutant phenotypes. Our findings elaborate on the sensitivity of HIV-2 CA to chemical conditions and reveal that it assembles into a more varied spectrum of particle morphologies compared to HIV-1. Utilizing these assemblies, we tested the hypothesis that HIV-1 and HIV-2 employ divergent mechanisms to stabilize CA oligomer forms and investigate the effects of non-conserved substitutions at the CA inter-protomer interfaces. This work advances our understanding of the key biochemical determinants of HIV-2 CA assembly that are distinct from HIV-1 and may contribute to their divergent virological properties. Full article

(This article belongs to the Special Issue Structural and Mechanistic Advances in Retroviral Biology)

► Show Figures

Figure 1

20 pages, 7656 KB

Open AccessArticle

Predicting the Landscape Epidemiology of Foot-and-Mouth Disease in Endemic Regions: An Interpretable Machine Learning Approach

by Moh A. Alkhamis, Hamad Abouelhassan, Abdulaziz Alateeqi, Abrar Husain, John M. Humphreys, Jonathan Arzt and Andres M. Perez

Viruses 2025, 17(10), 1383; https://doi.org/10.3390/v17101383 - 17 Oct 2025

Viewed by 490

Abstract

Foot-and-mouth disease (FMD) remains a devastating threat to livestock health and food security in the Middle East and North Africa (MENA), where complex interactions among host, environmental, and anthropogenic factors constitute an optimal endemic landscape for virus circulation. Here, we applied an interpretable [...] Read more.

Foot-and-mouth disease (FMD) remains a devastating threat to livestock health and food security in the Middle East and North Africa (MENA), where complex interactions among host, environmental, and anthropogenic factors constitute an optimal endemic landscape for virus circulation. Here, we applied an interpretable machine learning (ML) statistical framework to model the epidemiological landscape of FMD between 2005 and 2025. Furthermore, we compared the ecological niche of serotypes O and A in the MENA region. Our ML algorithms demonstrated high predictive performance (accuracies > 85%) in identifying the geographical extent of high-risk areas, including under-reported regions such as the Southern and Northeastern Arabian Peninsula. Sheep density emerged as the dominant predictor for all FMD outbreaks and serotype O, with significant non-linear relationships with wind, temperature, and human population density. In contrast, serotype A risk was primarily influenced by buffalo density and proximity to roads and cropland. Our in-depth interaction and Shapley value analyses provided fine-scale interpretability by interrogating the threshold effects of each feature in shaping the spatial risk of FMD. Further implementation of our analytical pipeline to guide risk-based surveillance programs and intervention efforts will help reduce the economic and public health impacts of this devastating animal pathogen. Full article

(This article belongs to the Special Issue Advances in Endemic and Emerging Viral Diseases in Livestock: 2nd Edition)

► Show Figures

Figure 1

19 pages, 2601 KB

Open AccessReview

Oropouche Virus: An Overview of the Current Status of Diagnostics

by Daniele Lapa, Maria Anele Romeo, Alessandra Spina, Eliana Specchiarello and Fabrizio Maggi

Viruses 2025, 17(10), 1382; https://doi.org/10.3390/v17101382 - 17 Oct 2025

Viewed by 458

Abstract

The Orthobunyavirus Oropouche (OROV) has become an urgent public health threat in Central and South America, as well as in other countries worldwide. Since its initial identification, there have been over 30 outbreaks, with the largest reported in late 2024 in Brazil. This [...] Read more.

The Orthobunyavirus Oropouche (OROV) has become an urgent public health threat in Central and South America, as well as in other countries worldwide. Since its initial identification, there have been over 30 outbreaks, with the largest reported in late 2024 in Brazil. This outbreak prompted an epidemiological alert due to a significant increase in OF cases in non-Amazonian states in the Americas region, as well as in European countries, where 44 imported cases were identified. Humans become infected predominantly through the bite of the Culicoides paraensis midge, and the symptoms could be misinterpreted due to their similarity to those of other arboviral infections. Due to the lack of a point-of-care test, RT-qPCR is currently the key diagnostic test during the acute phase of the disease. This review focuses primarily on the available molecular and serological diagnostic methods. The latter could indeed be used as a confirmation test to monitor the patient’s immunological status and better distinguish between cross-reacting arboviruses. In addition, this review explains also the existing sequencing methods required to enforce the surveillance system for OROV reassortant species that could cause a new worldwide outbreak. The information gathered could provide a valuable basis for implementing additional surveillance systems in those countries lacking up-to-date data. Full article

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

► Show Figures

Figure 1

21 pages, 3312 KB

Open AccessArticle

Acute HIV Infection and ART Response: Insights into T Cell Subsets, Activation, Exhaustion, and Blood and GALT HIV Reservoir

by Soraia Santana de Moura, Diogo Gama Caetano, Monick Lindenmeyer Guimarães, Rayana Katylin Mendes da Silva, Natasha Cabral, Simone da Costa Cruz Silva, Marcelo Ribeiro-Alves, Sylvia L. M. Teixeira, Ingebourg Georg, Desirée Vieira Gomes dos Santos, Sandro Nazer, Rafael Teixeira Fraga, Brenda Hoagland, Larissa Villela, Beatriz Gilda Jegerhorn Grinsztejn, Valdiléa Gonçalves Veloso, Fernanda Heloise Côrtes and Sandra W. Cardoso

Viruses 2025, 17(10), 1381; https://doi.org/10.3390/v17101381 - 16 Oct 2025

Viewed by 400

Abstract

Investigating immunological and viral reservoir dynamics in blood and GALT during acute HIV phase advances understanding of HIV persistence. Dynamics of T cells and HIV reservoirs immediately after early ART require further investigation. We evaluated the ART impact at 12 (M12) and 24 [...] Read more.

Investigating immunological and viral reservoir dynamics in blood and GALT during acute HIV phase advances understanding of HIV persistence. Dynamics of T cells and HIV reservoirs immediately after early ART require further investigation. We evaluated the ART impact at 12 (M12) and 24 months (M24) on immunological, virological and reservoir markers of 24 participants starting ART at Fiebig ≤ V (Baseline = D0) in a Brazilian cohort. We measured the frequency of T cell activation, exhaustion, memory subsets, Th17 and pTfh cells by flow cytometry and quantified total HIV DNA by qPCR in PBMC and GALT. Most participants were cisgender MSM (95.9%), with a median age of 27 years (IQR 25–36). At enrollment (D0), four participants used triple ART as PEP, and two were under oral PrEP and they exhibited higher CD4/CD8 ratios. Higher CD4/CD8 ratios were also observed in participants classified as Fiebig I to III. A total of 92% achieved viral suppression at M12 and 96% at M24. CD4 counts rose from 646 to 861 cells/mm³, and the CD4/CD8 ratio improved from 0.76 to 1.24 (p < 0.01). HIV DNA in PBMCs decreased 4-fold by M12 and 61-fold by M24, with 50% of participants reaching undetectable levels by M24 (p < 0.01). In GALT, undetectable HIV DNA increased from 27% at D0 to 75% at M12. HIV DNA in PBMCs and GALT correlated with plasma VL, while the CD4/CD8 ratio was inversely linked to PBMC reservoirs (rho = −0.66; p < 0.05). Early ART reduced activated CD8⁺ T cells (p < 0.05) but had minimal effects on CD4⁺ T cells or exhaustion markers. By M24, CD8⁺ TCM increased, and CD8⁺ TEF decreased (p < 0.01), while Th17 and pTfh levels remained stable. Early ART led to viral suppression and immune restoration, and influenced reservoir dynamics. The CD4/CD8 ratio was shown to be a key marker of early treatment success. Since a quarter of the participants were identified while initiating PrEP/PEP, it is important to consider the acute phase window according to vulnerability. Recent PEP/PrEP use often excludes participants from clinical trials on bNAbs and therapeutic vaccines targeting viral reservoirs during the acute phase of HIV. Since these are the populations that may benefit from these strategies, larger studies including those people are needed. Full article

(This article belongs to the Special Issue HIV Reservoirs, Latency, and the Factors Responsible)

► Show Figures

Figure 1

12 pages, 2917 KB

Open AccessArticle

Different Susceptibility of Mammalian Cell Lines to Severe Fever with Thrombocytopenia Syndrome Virus Infection

by Marla Anggita, Samuel Nyampong, Weiyin Hu, Hiroshi Shimoda and Daisuke Hayasaka

Viruses 2025, 17(10), 1380; https://doi.org/10.3390/v17101380 - 16 Oct 2025

Viewed by 447

Abstract

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging tick-borne infectious disease that poses a significant public health threat. SFTS virus (SFTSV) has a broad host range, including humans, cats, and natural reservoir species. Therefore, cultured cell lines derived from different mammalian species [...] Read more.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging tick-borne infectious disease that poses a significant public health threat. SFTS virus (SFTSV) has a broad host range, including humans, cats, and natural reservoir species. Therefore, cultured cell lines derived from different mammalian species are useful for understanding the susceptibility of SFTSV in hosts. In this study, we evaluated pathogenicity and infectivity, focusing on cytopathic effect (CPE) induction and growth kinetics of SFTSV in several mammalian cell lines, including our original tiger-derived TLT, wild deer–derived DFKT and DFLT, and hedgehog-derived HHoVT. Following SFTSV infection, TLT, CRFK (cat), FCWF-4 (cat), and CPK (porcine) cells exhibited CPE, whereas Vero E6 (monkey), A549 (human), BHK-21 (hamster), DFKT, DFLT, and HHoVT cells did not. Infectious viral yields in the supernatants of TLT, CRFK, FCWF-4, Vero E6, and BHK-21 were higher than those of CPK, A549, DFLT, and DFKT. SFTSV infection in hedgehog-derived HHoVT cells was very limited. These observations suggest that features such as viral CPE and virus yield following SFTSV infection depend on cell type. It is noteworthy that TLT formed clear plaques that were easy to count, indicating that TLT cells are useful for the titration of infectious SFTSV by plaque-forming assay. Our results provide useful information and tools for further elucidating the mechanisms of SFTSV infectivity, proliferation, and pathogenicity using in vitro models. Full article

(This article belongs to the Section Animal Viruses)

► Show Figures

Figure 1

11 pages, 1097 KB

Open AccessCase Report

Refractory CMV Enteritis in Small Bowel Transplantation: A Case Highlighting the Challenges of Balancing Immunosuppression and Novel Antiviral Therapies

by Abdulrahman A. Al-Saud, Ehab H. Abufarhaneh, Madain S. Alsanea, Reem M. Alameer, Amani H. Yamani, Fatimah S. Alhamlan and Reem S. Almaghrabi

Viruses 2025, 17(10), 1379; https://doi.org/10.3390/v17101379 - 15 Oct 2025

Viewed by 446

Abstract

Background: Cytomegalovirus (CMV) remains a formidable complication in small bowel transplantation (SBT) due to the graft’s high immunogenicity and profound immunosuppression required, with refractory disease representing a particularly devastating challenge. Case: We report an 18-year-old male who underwent SBT, complicated by recurrent acute [...] Read more.

Background: Cytomegalovirus (CMV) remains a formidable complication in small bowel transplantation (SBT) due to the graft’s high immunogenicity and profound immunosuppression required, with refractory disease representing a particularly devastating challenge. Case: We report an 18-year-old male who underwent SBT, complicated by recurrent acute rejection episodes requiring intensive immunosuppression. He developed refractory CMV disease, marked by non-response to first line therapy with ganciclovir—despite the absence of genotypic resistance—necessitating sequential use of foscarnet, dual antivirals, CMV immunoglobulin, and novel agents (maribavir and letermovir). Discussion: This case illustrates the multifactorial drivers of refractory CMV disease in SBT recipients, including donor–recipient serostatus mismatch, profound immunosuppression through T-cell-depleting induction, corticosteroid exposure, and biologic therapy. It highlights the distinction between refractory and resistant CMV, and the role of combination antiviral strategies including novel agents to achieve disease control. Outcomes remain dismal despite aggressive and innovative therapies, underscoring the limited efficacy of interventions in the context of severe immunologic compromise. Conclusions: Refractory CMV enteritis in SBT exemplifies the extreme difficulty of balancing viral control with rejection management. Despite exhausting antiviral strategies, survival remains poor. Highlights: Refractory CMV enteritis is a significant challenge in small bowel transplant recipients due to intense immunosuppression. Persistent CMV disease may occur despite antiviral prophylaxis and the absence of resistant gene mutations. Combination antiviral strategies, including maribavir, demonstrated significant clinical improvement. Profound immunosuppression required to manage acute graft rejection episodes complicates antiviral management and disease clearance. Despite best efforts in CMV management in this population, outcomes may still be compromised by unrelated or compounding factors. Full article

(This article belongs to the Special Issue Human Cytomegalovirus Therapeutic Strategies and Clinical Applications)

► Show Figures

Figure 1

29 pages, 4482 KB

Open AccessArticle

Quantifying the Inhibitory Efficacy of HIV-1 Therapeutic Interfering Particles at a Single CD4 T-Cell Resolution

by Igor Sazonov, Dmitry Grebennikov, Rostislav Savinkov, Andreas Meyerhans and Gennady Bocharov

Viruses 2025, 17(10), 1378; https://doi.org/10.3390/v17101378 - 15 Oct 2025

Viewed by 393

Abstract

Efficient control of HIV-1 infection relies on highly active antiretroviral therapy (HAART). However, this therapy is not curative and requires continuous drug administration. Application of HIV-1 defective interfering particles (DIPs), engineered with ablations in key viral protein expressions (e.g., Tat, Rev, Vpu, and [...] Read more.

Efficient control of HIV-1 infection relies on highly active antiretroviral therapy (HAART). However, this therapy is not curative and requires continuous drug administration. Application of HIV-1 defective interfering particles (DIPs), engineered with ablations in key viral protein expressions (e.g., Tat, Rev, Vpu, and Env), suggests a therapeutic potential transforming them into Therapeutic Interfering Particles (TIPs). A recent animal HIV model study in non-human primates reports a substantial reduction in viral load after a single intravenous injection of TIPs. In contrast, human clinical trials demonstrate no beneficial effect of defective interfering particles (DIPs) in people living with HIV-1. This discrepancy highlights the importance of further investigation of HIV-TIP interactions. A quantitative view of intracellular replication for HIV-1 in the presence of TIPs is still missing. Here, we develop a high-resolution mathematical model to study various aspects of the interference of a specific engineered TIP-2 particle characterized by a 2.5-kb deletion in the HIV pol-vpr region with HIV-1 replication within infected CD4+ T cells. We define the conditions in terms of the number of homozygous HIV-1 virions and TIP-2 particles that enable the reduction of the wild-type virus replication number to the value of about one. The deterministic model predicts that at a ratio of 1 HIV-1 to 10 TIP-2 particles, the infected cell still produces some viruses, although in a minor quantity, i.e., about two virions per cycle. Pre-activation of the interferon type I (IFN-I) system results in a complete block of HIV-1 production by TIP-2 co-infected cells. Overall, the modelling results suggest that to improve the effectiveness of TIPs in reducing HIV infection, their combination with other types of antiviral protection should be considered. Our results can be used in the development of combination therapy aimed at treating HIV-1 infection. Full article

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

► Show Figures

Figure 1

11 pages, 1157 KB

Open AccessSystematic Review

Impact of Vaccinating Adult Women Who Are HPV-Positive or with Confirmed Cervical SIL with the 9-Valent Vaccine—A Systematic Review

by Dominik Pruski, Sonja Millert-Kalińska, Robert Jach, Jakub Żurawski and Marcin Przybylski

Viruses 2025, 17(10), 1377; https://doi.org/10.3390/v17101377 - 15 Oct 2025

Viewed by 615

Abstract

Infection with oncogenic human papillomavirus (HPV) remains a leading cause of cervical cancer and other HPV-related diseases. This situation persists despite the availability of effective prophylactic vaccines. While global vaccination programs have significantly reduced the incidence of HPV in adolescents and young adults, [...] Read more.

Infection with oncogenic human papillomavirus (HPV) remains a leading cause of cervical cancer and other HPV-related diseases. This situation persists despite the availability of effective prophylactic vaccines. While global vaccination programs have significantly reduced the incidence of HPV in adolescents and young adults, many women presenting with HPV infection or squamous intraepithelial lesions (SIL) were not covered by primary prevention. This review was performed with the aim of evaluating the impact of administering the 9-valent HPV vaccine in adult women who are HPV-positive or have histologically confirmed cervical precancerous lesions. Following the PRISMA 2020 guidelines, a search was performed in the MEDLINE, Scopus, and Cochrane Library databases. A total of 653 studies were retrieved, of which 7 studies, including 19,414 women, met the inclusion criteria. According to the literature, vaccination was linked to significant reductions in persistent HPV infection, progression of SIL, and recurrence of high-grade lesions after surgical removal. Complete HPV remission was achieved in up to 72.4% of vaccinated women, compared to 45.7% among unvaccinated controls. Vaccination after conization lowered the recurrence risk of CIN2+ lesions by 87%, with benefits seen regardless of timing. The most significant effect was observed when vaccine administration was performed before the surgical procedure. Furthermore, HPV vaccination notably enhanced viral clearance and decreased the likelihood of repeated surgical interventions. Despite differences in study design and follow-up definitions, the overall evidence supports additional vaccination in HPV-positive adult women as an effective measure to reduce recurrence and promote viral remission. These findings emphasize the need for clear guidelines and wider access to HPV vaccination for adult populations. Full article

(This article belongs to the Special Issue Viral Infections in Gynecological Diseases)

► Show Figures

Figure 1

14 pages, 1952 KB

Open AccessArticle

Genetic and Serological Analysis of H7N3 Avian Influenza Viruses in Mexico for Pandemic Risk Assessment

by Guadalupe Ayora-Talavera, Irma López-Martínez, Gisela Barrera-Badillo, Rodrigo Aparicio-Antonio, Nidia Aréchiga-Ceballos, Anita Aguirre-Barbosa, Rosa Maria Wong-Chew, Daniel Canul-Canul and Mario Solís-Hernández

Viruses 2025, 17(10), 1376; https://doi.org/10.3390/v17101376 - 15 Oct 2025

Viewed by 489

Abstract

Avian influenza A viruses pose ongoing threats to human and animal health, with H7 subtypes causing outbreaks globally. In Mexico, highly pathogenic H7N3 viruses have circulated in poultry since 2012, causing sporadic human infections. Here we analyzed genetic markers in hemagglutinin sequences from [...] Read more.

Avian influenza A viruses pose ongoing threats to human and animal health, with H7 subtypes causing outbreaks globally. In Mexico, highly pathogenic H7N3 viruses have circulated in poultry since 2012, causing sporadic human infections. Here we analyzed genetic markers in hemagglutinin sequences from Mexican H7N3 isolates and conducted serological assays on human populations with poultry exposure. Our results show conserved avian-like receptor binding sites, thus limiting human adaptation, alongside antigenic drift and acquisition of glycosylation sites likely driven by vaccination. Serological testing of 1103 individuals revealed no detectable antibodies against H7N3, indicating a naïve population. Phylogenetic analyses revealed multiple virus clades circulating regionally. These findings suggest that while current H7N3 viruses have limited capacity for sustained human transmission, the lack of population immunity underscores the importance of continued surveillance and risk assessment to mitigate potential pandemic threats. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Evolution, and Transmission of Avian Influenza Viruses)

► Show Figures

Figure 1

16 pages, 250 KB

Open AccessArticle

Behavioral Predictors of Intentional and Unintentional Nonadherence to Antiretroviral Therapy and Their Implications for Virological Failure Among People with HIV in Taiwan

by Su-Han Hsu, Chien-Chun Wang, Yung-Feng Yen, Tsen-Fang Yen, Po-Tsen Yeh and Hsin-Hao Lai

Viruses 2025, 17(10), 1375; https://doi.org/10.3390/v17101375 - 14 Oct 2025

Viewed by 540

Abstract

Adherence to antiretroviral therapy (ART) is critical for HIV management and sustained virological suppression. Differentiating intentional from unintentional nonadherence is essential for developing tailored interventions, yet evidence from Asian populations remains limited. A cross-sectional study of 846 people with HIV (PWH) in northern [...] Read more.

Adherence to antiretroviral therapy (ART) is critical for HIV management and sustained virological suppression. Differentiating intentional from unintentional nonadherence is essential for developing tailored interventions, yet evidence from Asian populations remains limited. A cross-sectional study of 846 people with HIV (PWH) in northern Taiwan assessed ART adherence using the MARS-5 scale. Participants were categorized into good, unintentional, or intentional non-adherence groups. Logistic regression identified associated behavioral and psychosocial factors. Recreational drug use and younger age were independently linked to both unintentional and intentional poor adherence. Higher income and the use of single-tablet regimens were protective against intentional nonadherence, whereas disclosure of HIV status to a partner and an unsuppressed viral load were significantly associated with intentional nonadherence. Reported reasons included being too busy, emotional distress, and running out of medication. These findings suggest that intentional and unintentional nonadherence represent distinct behavioral patterns, with intentional lapses more strongly linked to virological failure. Addressing substance use, simplifying regimens, and providing psychosocial support after disclosure are essential to optimize adherence and achieve UNAIDS 2030 targets. Full article

(This article belongs to the Special Issue Advances in Research on HIV Drug Resistance and Other Determinants of Treatment Success: 3rd Edition)

13 pages, 848 KB

Open AccessArticle

Epidemiology and Evolution of Bovine Viral Diarrhea Virus (BVDV) in Uruguay: A 10-Year Study

by Leticia Maya, Matias Castells, Caroline Silveira, Federico Giannitti, Ingryd Merchioratto, Maria Barrandeguy, Alejo Menchaca and Rodney Colina

Viruses 2025, 17(10), 1374; https://doi.org/10.3390/v17101374 - 14 Oct 2025

Viewed by 535

Abstract

Bovine viral diarrhea virus (BVDV) is a pathogen of worldwide economic importance. In Uruguay, BVDV is endemic, with seroprevalence >80% at the farm level. This study analyzed 912 samples collected from January 2018 to October 2024 by reverse transcription PCR and sequencing, from [...] Read more.

Bovine viral diarrhea virus (BVDV) is a pathogen of worldwide economic importance. In Uruguay, BVDV is endemic, with seroprevalence >80% at the farm level. This study analyzed 912 samples collected from January 2018 to October 2024 by reverse transcription PCR and sequencing, from calves with diarrhea, aborted fetuses, heifers with a history of abortions, and animals exhibiting symptoms of Mucosal Disease. This work summarizes ten years (2014–2024) of molecular epidemiology and evolution of BVDV. Analysis of the BVDV 5′UTR/N^pro genomic region revealed that the BVDV-1a, 1e, 1i, and 2b subtypes circulate in Uruguay. BVDV-1a remains the most prevalent subtype, followed by BVDV-2b, whose prevalence has been increasing. Our previous studies revealed that BVDV-1a showed geographical diversification in Uruguay. In this work, evolutionary studies conducted with N^pro genomic region showed that BVDV-2b is evolving at a substitution rate of 6.09 × 10⁻⁴ substitutions/site/year and has been introduced from Brazil in six separate events between 1870 and 1928, showing no geographical diversification. This work demonstrates that BVDV-1a and BVDV-2b are evolving differently in Uruguay. This evolutionary divergence is notable when comparing patterns observed in other countries where these subtypes circulate. Our findings provide crucial knowledge that should be considered for developing effective BVDV control measures in Uruguay. Full article

(This article belongs to the Special Issue Bovine Viral Diarrhea Viruses and Other Pestiviruses)

► Show Figures

Figure 1

21 pages, 4481 KB

Open AccessArticle

An Intranasal Challenge Model in African Green Monkeys (Chlorocebus aethiops) for Mild-to-Moderate COVID-19 Disease Caused by Subvariant XBB.1.5

by Nadia Storm, Ming Lo, Nicholas Crossland, Margaux Seyler-Schmidt, Hilary Staples, Daniela Silva-Ayala, Ambre M. Laprise, Lauren St. Denis, Kyle Grosz, Aoife O’Connell, Hans Gertje, Tillie Ripin, Claire Decker, M. Mazur, Colleen Thurman, Marlene Espinoza, Gavin Morrow, Christopher L. Parks, Christopher L. Cooper and Anthony Griffiths

Viruses 2025, 17(10), 1373; https://doi.org/10.3390/v17101373 - 14 Oct 2025

Viewed by 416

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily causes mild to moderate respiratory illness in humans, but infection can also lead to long-term complications, including chronic fatigue, respiratory and cardiac issues, or even death. In November 2021, the emergence of the highly transmissible [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily causes mild to moderate respiratory illness in humans, but infection can also lead to long-term complications, including chronic fatigue, respiratory and cardiac issues, or even death. In November 2021, the emergence of the highly transmissible Omicron variant marked a significant shift in the pandemic, with its subvariants rapidly spreading and continuing to evolve worldwide. The continuing introduction of Omicron subvariants underscores the need for the development of up-to-date vaccines, as well as for appropriate animal models in which they can be evaluated. Among these subvariants, XBB.1.5 stands out for its ability to evade the immune response from previous infection or vaccination. The objective of this study was to determine the disease course in African green monkeys (AGMs) following intranasal exposure to the XBB.1.5 subvariant. In four intranasally exposed AGMs, histopathological findings in the lungs consistent with SARS-CoV-2 infection included lymphohistiocytic and neutrophilic bronchiolitis with variable numbers of syncytial cells, to terminal bronchiole-centric, bronchointerstitial pneumonia with alveolar type II (AT2) pneumocyte hyperplasia, with evidence of acute alveolar injury, including alveolar septal necrosis and hyaline membrane formation. The two males showed more severe pneumonia compared to the two females. SARS-CoV-2 RNA was detected in the lungs or tracheobronchial lymph nodes in the males but not in the females, which correlated with higher cumulative lung pathology scores in the males. In the females, SARS-CoV-2 RNA was limited to the colon and nasal turbinates. Our results indicate that AGMs exhibit a disease course similar to most humans when exposed intranasally, making them a suitable model for studying mild to moderate SARS-CoV-2 infection. Therefore, further work is warranted to determine if this model could have utility for the evaluation of vaccine and therapeutic candidates against contemporary SARS-CoV-2 variants. Full article

(This article belongs to the Section Coronaviruses)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Viruses, Volume 17, Issue 10 (October 2025) – 118 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI