Viruses

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

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)

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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

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)

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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

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)

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18 pages, 4514 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

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)

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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

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)

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22 pages, 2310 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

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)

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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

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)

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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

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)

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20 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

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)

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11 pages, 648 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

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)

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

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)

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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

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)

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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

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))

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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

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)

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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

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)

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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

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)

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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

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 rate 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)

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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

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)

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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

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)

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