Viruses

26 pages, 1443 KiB

Open AccessReview

Bacteriophages as Agents for Plant Disease Control: Where Are We After a Century?

by Manoj Choudhary, Ibukunoluwa A. Bankole, Sophia T. McDuffee, Apekshya Parajuli, Mousami Poudel, Botond Balogh, Mathews L. Paret and Jeffrey B. Jones

Viruses 2025, 17(8), 1033; https://doi.org/10.3390/v17081033 - 23 Jul 2025

Abstract

The rise in antibiotic-resistant bacteria has made the management of bacterial diseases increasingly challenging. As a result, bacteriophages have gained attention as a promising alternative to antibiotics for combating bacterial pathogens. However, the usage of phages as biocontrol agents faces many challenges, including [...] Read more.

The rise in antibiotic-resistant bacteria has made the management of bacterial diseases increasingly challenging. As a result, bacteriophages have gained attention as a promising alternative to antibiotics for combating bacterial pathogens. However, the usage of phages as biocontrol agents faces many challenges, including environmental stability, delivery efficiency, host specificity, and potential bacterial resistance. Advancements in genetic engineering and nanotechnology have been explored to enhance the stability, efficacy, and adaptability of phage-based treatments. In this review, we discuss the key barriers to the effective implementation of phage therapy and highlight innovative strategies to overcome these challenges. By addressing these limitations, this review aims to provide insights into optimizing phage-based approaches for widespread therapeutic and biocontrol applications. Full article

(This article belongs to the Special Issue Bacteriophage-Based Biocontrol in Agriculture, 2nd Edition)

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11 pages, 659 KiB

Open AccessArticle

Afrina barna-like Virus, a Novel Virus Associated with Afrina sporoboliae, the Drop Seed Gall-Forming Nematode

by Edison Reyes-Proaño, Anna M. Griffin, Aida Duarte, Hongyan Sheng, Brenda K. Schroeder, Timothy D. Murray and Alexander V. Karasev

Viruses 2025, 17(8), 1032; https://doi.org/10.3390/v17081032 - 23 Jul 2025

Abstract

A novel barna-like virus was found to be associated with field-collected Afrina sporoboliae plant-parasitic nematodes. The positive-sense, single-stranded RNA genome of this virus, named Afrina barna-like virus (AfBLV), comprises 4020 nucleotides encoding four open reading frames (ORFs). ORF 1 encodes a protein product [...] Read more.

A novel barna-like virus was found to be associated with field-collected Afrina sporoboliae plant-parasitic nematodes. The positive-sense, single-stranded RNA genome of this virus, named Afrina barna-like virus (AfBLV), comprises 4020 nucleotides encoding four open reading frames (ORFs). ORF 1 encodes a protein product spanning a transmembrane, a peptidase, and VPg domains, whereas an overlapping ORF 2 encodes an RNA-dependent RNA polymerase (RdRP). ORF2 may be expressed via a −1 translational frameshift. In phylogenetic reconstructions, the RdRP of AfBLV was placed inside a separate clade of barna and barna-like viruses related to but distinct from the genera in the Solemoviridae and Alvernaviridae families, within the overall lineage of Sobelivirales. ORF 3 of AfBLV encodes a protein product of 206 amino acids (aa) long with homology to a putative protein encoded by a similarly positioned gene of an uncharacterized virus sequence identified previously as Barnaviridae sp. ORF 4 encodes a 161 aa protein with no significant similarities to sequences in the GenBank databases. AfBLV is the first barnavirus found in a nematode. Sequence comparisons of the AfBLV genome and genomes of other barna-like viruses suggested that a recombination event was involved in the evolution of AfBLV. Analyses of the phylogeny of RdRPs and genome organizations of barna-like and solemo-like viruses support the re-classification of Barnavirus and Dinornavirus genera as members of the Solemoviridae family. Full article

(This article belongs to the Special Issue Diversity and Evolution of Viruses in Ecosystem 2025)

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14 pages, 1022 KiB

Open AccessArticle

Pathology, Tissue Distribution, and Phylogenetic Characterization of Largemouth Bass Virus Isolated from a Wild Smallmouth Bass (Micropterus dolomieu)

by Christine J. E. Haake, Thomas B. Waltzek, Chrissy D. Eckstrand, Nora Hickey, Joetta Lynn Reno, Rebecca M. Wolking, Preeyanan Sriwanayos, Jan Lovy, Elizabeth Renner, Kyle R. Taylor and Ryan Oliveira

Viruses 2025, 17(8), 1031; https://doi.org/10.3390/v17081031 - 23 Jul 2025

Abstract

We performed a diagnostic disease investigation on a wild smallmouth bass (Micropterus dolomieu) with skin ulcers that was collected from Lake Oahe, South Dakota, following reports from anglers of multiple fish with similar lesions. Gross and histologic lesions of ulcerative dermatitis, [...] Read more.

We performed a diagnostic disease investigation on a wild smallmouth bass (Micropterus dolomieu) with skin ulcers that was collected from Lake Oahe, South Dakota, following reports from anglers of multiple fish with similar lesions. Gross and histologic lesions of ulcerative dermatitis, myositis, and lymphocytolysis within the spleen and kidneys were consistent with largemouth bass virus (LMBV) infection. LMBV was detected by conventional PCR in samples of a skin ulcer, and the complete genome sequence of the LMBV (99,184 bp) was determined from a virus isolate obtained from a homogenized skin sample. A maximum likelihood (ML) phylogenetic analysis based on the major capsid protein (MCP) gene alignment supported the LMBV isolate (LMBV-SD-2023) as a member of the species Ranavirus micropterus1, branching within the subclade of LMBV isolates recovered from North American largemouth (Micropterus salmoides) and smallmouth bass. This is the first detection of LMBV in wild smallmouth bass from South Dakota. The ultrastructure of the LMBV isolate exhibited the expected icosahedral shape of virions budding from cellular membranes. Viral nucleic acid in infected cells was visualized via in situ hybridization (ISH) within dermal granulomas, localized predominantly at the margin of epithelioid macrophages and central necrosis. Further sampling is needed to determine the geographic distribution, affected populations, and evolutionary relationship between isolates of LMBV. Full article

(This article belongs to the Special Issue Iridoviruses, 2nd Edition)

15 pages, 1838 KiB

Open AccessArticle

Association of Comorbidities with Adverse Outcomes in Adults Hospitalized with Respiratory Syncytial Virus (RSV) Infection: A Retrospective Cohort Study from Switzerland (2022–2024)

by Neetha Joseph, Elisa D. Bally-von Passavant, Giorgia Lüthi-Corridori, Fabienne Jaun, Sandra Mitrovic, Jörg Daniel Leuppi and Maria Boesing

Viruses 2025, 17(8), 1030; https://doi.org/10.3390/v17081030 - 23 Jul 2025

Abstract

Introduction: Respiratory Syncytial Virus (RSV) infection causes seasonal respiratory illness in both children and adults, with increasing recognition of its impact in older adults with chronic comorbidities. This study aimed to characterize adult patients hospitalized with RSV infection in Switzerland and identify comorbidities [...] Read more.

Introduction: Respiratory Syncytial Virus (RSV) infection causes seasonal respiratory illness in both children and adults, with increasing recognition of its impact in older adults with chronic comorbidities. This study aimed to characterize adult patients hospitalized with RSV infection in Switzerland and identify comorbidities linked to poor outcomes. Methods: Adults hospitalized with RSV infection between May 2022 and April 2024 at a Swiss public teaching hospital were included in this retrospective observational study. To assess the association between comorbidities and patient outcomes, separate multivariable regression analyses for each comorbidity, adjusted for age and sex, were performed. The primary composite endpoint was ’severe course’ (in-hospital death or intensive care unit (ICU) admission), secondary endpoints included in-hospital death, ICU admission, and length of stay. Results: Among 136 included patients (mean age 78, 38% male), 98% had comorbidities, most commonly cardiovascular (75.7%), respiratory (51%), and chronic kidney disease (CKD) (36.7%). Further, 18.4% experienced a severe course. The ICU admission rate was 14.0%, in-hospital mortality 6.6%, and the median hospital stay of survivors was 6 days (IQR 4–10). CKD was significantly associated with severe course (OR 2.64, p = 0.045) and in-hospital mortality (OR 11.6, p = 0.025), while immunosuppression predicted ICU admission (OR 5.7, p = 0.018). Length of stay was not linked to any comorbidities. Conclusions: In this cohort of hospitalized adults, mainly elderly individuals with chronic comorbidities were tested positive for RSV. CKD and immunosuppression were associated with severe course. Prevention strategies, including RSV vaccination, should prioritize these high-risk populations. Full article

(This article belongs to the Special Issue RSV Epidemiological Surveillance: 2nd Edition)

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28 pages, 5780 KiB

Open AccessArticle

Multiscale Modeling and Dynamic Mutational Profiling of Binding Energetics and Immune Escape for Class I Antibodies with SARS-CoV-2 Spike Protein: Dissecting Mechanisms of High Resistance to Viral Escape Against Emerging Variants

by Mohammed Alshahrani, Vedant Parikh, Brandon Foley and Gennady Verkhivker

Viruses 2025, 17(8), 1029; https://doi.org/10.3390/v17081029 - 23 Jul 2025

Abstract

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding [...] Read more.

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope footprint and distributed hotspot architecture, additionally supported by backbone-mediated specific interactions, which are less sensitive to amino acid substitutions and together enable exceptional tolerance to mutational escape. In contrast, BD-604 and OMI-42 exhibit localized binding modes with strong dependence on side-chain interactions, rendering them particularly vulnerable to escape mutations at K417N, L455M, F456L and A475V. Similarly, P5S-1H1 and P5S-2B10 display intermediate behavior—effective in some contexts but increasingly susceptible to antigenic drift due to narrower epitope coverage and concentrated hotspots. Our computational predictions show strong agreement with experimental deep mutational scanning data, validating the accuracy of the models and reinforcing the value of binding hotspot mapping in predicting antibody vulnerability. This work highlights that neutralization breadth and durability are not solely dictated by epitope location, but also by how binding energy is distributed across the interface. The results provide atomistic insight into mechanisms driving resilience to immune escape for broadly neutralizing antibodies targeting the ACE2 binding interface—which stems from cumulative effects of structural diversity in binding contacts, redundancy in interaction patterns and reduced vulnerability to mutation-prone positions. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Approaches in Viral Genomics and Evolution 2025)

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17 pages, 4093 KiB

Open AccessArticle

4-Hydroxychalcone Inhibits Human Coronavirus HCoV-OC43 by Targeting EGFR/AKT/ERK1/2 Signaling Pathway

by Yuanyuan Huang, Jieyu Li, Qiting Luo, Yuexiang Dai, Xinyi Luo, Jiapeng Xu, Wei Ye, Xinrui Zhou, Jiayi Diao, Zhe Ren, Ge Liu, Zhendan He, Zhiping Wang, Yifei Wang and Qinchang Zhu

Viruses 2025, 17(8), 1028; https://doi.org/10.3390/v17081028 - 23 Jul 2025

Abstract

Human coronaviruses are a group of viruses that continue to threaten human health. In this study, we investigated the antiviral activity of 4-hydroxychalcone (4HCH), a chalcone derivative, against human coronavirus HCoV-OC43. We found that 4HCH significantly inhibited the cytopathic effect, reduced viral protein [...] Read more.

Human coronaviruses are a group of viruses that continue to threaten human health. In this study, we investigated the antiviral activity of 4-hydroxychalcone (4HCH), a chalcone derivative, against human coronavirus HCoV-OC43. We found that 4HCH significantly inhibited the cytopathic effect, reduced viral protein and RNA levels in infected cells, and increased the survival rate of HCoV-OC43-infected suckling mice. Mechanistically, 4HCH targets the early stages of viral infection by binding to the epidermal growth factor receptor (EGFR) and inhibiting the EGFR/AKT/ERK1/2 signaling pathway, thereby suppressing viral replication. Additionally, 4HCH significantly reduced the production of pro-inflammatory cytokines and chemokines in both HCoV-OC43-infected RD cells and a suckling mouse model. Our findings demonstrate that 4HCH exhibits potent antiviral activity both in vitro and in vivo, suggesting its potential as a therapeutic agent against human coronaviruses. This study highlights EGFR as a promising host target for antiviral drug development and positions 4HCH as a candidate for further investigation in the treatment of coronavirus infections. Full article

(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))

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24 pages, 16011 KiB

Open AccessArticle

Novel Giant Phages vB_AerVM_332-Vera and vB_AerVM_332-Igor and Siphophage vB_AerVS_332-Yulya Infecting the Same Aeromonas veronii Strain

by Igor V. Babkin, Vera V. Morozova, Yuliya N. Kozlova, Valeria A. Fedorets, Artem Y. Tikunov, Tatyana A. Ushakova, Alevtina V. Bardasheva, Elena V. Zhirakovskaya and Nina V. Tikunova

Viruses 2025, 17(8), 1027; https://doi.org/10.3390/v17081027 - 22 Jul 2025

Abstract

Three novel Aeromonas phages vB_AerVS_332-Yuliya, vB_AerVM_332-Vera, and vB_AerVM_332-Igor and their host Aeromonas veronii CEMTC7594 were found in the same water + sediments sample collected in a freshwater pond. Complete genome sequencing indicated that vB_AerVS_332-Yuliya (43,584 bp) is a siphophage, whereas vB_AerVM_332-Vera (294,685 bp) [...] Read more.

Three novel Aeromonas phages vB_AerVS_332-Yuliya, vB_AerVM_332-Vera, and vB_AerVM_332-Igor and their host Aeromonas veronii CEMTC7594 were found in the same water + sediments sample collected in a freshwater pond. Complete genome sequencing indicated that vB_AerVS_332-Yuliya (43,584 bp) is a siphophage, whereas vB_AerVM_332-Vera (294,685 bp) and vB_AerVM_332-Igor (237,907 bp) are giant phages. The host strain can grow at temperatures from 5 °C to 37 °C with an optimum of 25–37 °C; siphophage vB_AerVS_332-Yuliya effectively reproduced at temperature ≤ 25 °C, the optimal temperature for giant phage vB_AerVM_332-Igor was 25 °C, and giant phage vB_AerVM_332-Vera infected host cells at 5–10 °C. The genomes of these phages differed significantly from known phages; their level of nucleotide identity and values of intergenomic similarity with the corresponding neighboring phages indicated that each of these phages is a member of a new genus/subfamily. Giant phage vB_AerVM_332-Vera is a member of the proposed Chimallinviridae family, which forms Cluster D of giant phages that possibly evolved from phages with shorter genomes. Giant phage vB_AerVM_332-Igor is part of Cluster E, the known members of which preserve the size of genomes. Phages from Cluster F, containing Aeromonas phages among others, show a gradual decrease and/or increase in genomes during evolution, which indicates different strategies for giant phages. Full article

(This article belongs to the Special Issue Bacteriophage Diversity, 2nd Edition)

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28 pages, 2072 KiB

Open AccessReview

Advances in Epstein–Barr Virus Detection: From Traditional Methods to Modern Technologies

by Yidan Sun, Shuyu Ling, Dani Tang, Meimei Yang and Chao Shen

Viruses 2025, 17(8), 1026; https://doi.org/10.3390/v17081026 - 22 Jul 2025

Abstract

The Epstein–Barr virus (EBV) is a prevalent virus linked to various diseases, including infectious mononucleosis (IM), nasopharyngeal carcinoma, and Hodgkin’s lymphoma. Over the past few decades, EBV diagnostic strategies have evolved significantly—progressing from traditional serological assays and histopathology to more sensitive and specific [...] Read more.

The Epstein–Barr virus (EBV) is a prevalent virus linked to various diseases, including infectious mononucleosis (IM), nasopharyngeal carcinoma, and Hodgkin’s lymphoma. Over the past few decades, EBV diagnostic strategies have evolved significantly—progressing from traditional serological assays and histopathology to more sensitive and specific molecular techniques such as nucleic acid amplification and high-throughput sequencing (HTS). While conventional methods remain valuable for their accessibility and established clinical use, they are often limited by sensitivity, speed, and multiplexing capability. In contrast, emerging technologies, including isothermal amplification, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based diagnostics, multi-omics integration, and AI-assisted analysis, have demonstrated great promise in improving diagnostic accuracy, speed, and applicability in diverse clinical settings, including point-of-care testing (POCT). This review systematically explores the historical development of EBV diagnostic technologies, highlighting key milestones and future trends in precision medicine and global health readiness. Full article

(This article belongs to the Special Issue EBV and Disease: New Perspectives in the Post COVID-19 Era)

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24 pages, 12430 KiB

Open AccessArticle

DNAJ Homolog Subfamily C Member 11 Stabilizes SARS-CoV-2 NSP3 to Promote Double-Membrane Vesicle Formation

by Shuying Chen, Shanrong Yang, Xiaoning Li, Junqi Xiang, Jiangyu Cai, Yaokai Wang, Qingqing Li, Na Zang, Jiaxu Wang, Jian Shang and Yushun Wan

Viruses 2025, 17(8), 1025; https://doi.org/10.3390/v17081025 - 22 Jul 2025

Abstract

Coronaviruses, particularly those classified as highly pathogenic species, pose a significant threat to global health. These viruses hijack host cellular membranes and proteins to facilitate their replication, primarily through the formation of replication organelles (ROs). However, the precise regulatory mechanisms underlying RO formation [...] Read more.

Coronaviruses, particularly those classified as highly pathogenic species, pose a significant threat to global health. These viruses hijack host cellular membranes and proteins to facilitate their replication, primarily through the formation of replication organelles (ROs). However, the precise regulatory mechanisms underlying RO formation remain poorly understood. To elucidate these mechanisms, we conducted mass spectrometry analyses, identifying interactions between the host protein DnaJ homolog subfamily C member 11 (DNAJC11) and the SARS-CoV-2 nonstructural protein 3 (NSP3) protein. Notably, results showed that DNAJC11 depletion reduces SARS-CoV-2 infection, indicating possible positive regulatory involvement. But the ectopic expression of DNAJC11 did not lead to marked alterations in immune or inflammatory responses. DNAJC11 enhanced NSP3 expression stability through endogenous apoptosis pathways and facilitated its interaction with NSP4, thereby promoting the formation of double-membrane vesicles (DMVs). Knockdown of DNAJC11 reduced DMV number and size, accompanied by dysregulation of the endoplasmic reticulum and mitochondria. However, supplementation with DNAJC11 restored both DMV number and size. These findings provide novel insights into the role of DNAJC11 as a host factor that modulates DMV formation and supports SARS-CoV-2 replication by targeting the NSP3 protein. This study advances our understanding of the molecular interactions between host and viral components and highlights DNAJC11 as a potential target for antiviral interventions. Full article

(This article belongs to the Section Coronaviruses)

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13 pages, 1726 KiB

Open AccessArticle

Assessment of Mammalian Scavenger and Wild White-Tailed Deer Activity at White-Tailed Deer Farms

by Alex R. Jack, Whitney C. Sansom, Tiffany M. Wolf, Lin Zhang, Michelle L. Schultze, Scott J. Wells and James D. Forester

Viruses 2025, 17(8), 1024; https://doi.org/10.3390/v17081024 - 22 Jul 2025

Abstract

White-tailed deer (Odocoileus virginianus) in the wild and on cervid farms have drawn the attention of state wildlife agencies and animal health agencies as Chronic Wasting Disease (CWD) has spread across North America. Deer farm regulations have been implemented to reduce [...] Read more.

White-tailed deer (Odocoileus virginianus) in the wild and on cervid farms have drawn the attention of state wildlife agencies and animal health agencies as Chronic Wasting Disease (CWD) has spread across North America. Deer farm regulations have been implemented to reduce direct contact between wild and farmed cervids; however, evidence suggests that indirect contact to infectious prions passed through the alimentary tracts of scavengers may be an important transmission pathway. The objective of this study was to characterize mammalian scavenger and wild deer activities associated with deer farms and link these activities with site-specific spatial covariates utilizing a network of camera traps, mounted to farm perimeter fences. We monitored each of 14 farms in Minnesota, Wisconsin, and Pennsylvania for two weeks during the summer, with a subset of farms also monitored in the winter and fall. Across all sites and seasons, we captured 749 observations of wildlife. In total, nine species were captured, with wild white-tailed deer accounting for over three quarters of observations. Despite the large number of wild deer observed, we found that interactions between wild and farmed deer at the fence line were infrequent (six direct contacts observed). In contrast, mammalian scavengers were frequently observed inside and outside of the fence. Supplementary cameras placed on deer feeders revealed higher observation rates of scavengers than those placed along fence lines, highlighting the potential for transmission of CWD through indirect contact via scavenger excreta. To evaluate associations between the number of observations of focal species with land-cover characteristics, two mixed-effects regression models were fitted, one model for scavengers and one for wild deer. Contrary to our hypothesis, landscape context did not have a strong impact on wildlife visitation. This suggests that farm location is less important than management practices, highlighting the need for future research into how farming practices impact rates of wildlife visitation onto cervid farms. Full article

(This article belongs to the Special Issue Chronic Wasting Disease: From Pathogenesis to Prevention)

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11 pages, 3684 KiB

Open AccessCase Report

Reactivated CMV Proctitis/Anitis Presenting as a Localized Proximal Anal Swelling and Anal Pain in a Diabetic Patient: Case Report and Literature Review

by Dua Abuquteish, Ayat Al Oqaily, Lama Bataineh and Bashar Khater

Viruses 2025, 17(8), 1023; https://doi.org/10.3390/v17081023 - 22 Jul 2025

Abstract

Background: Cytomegalovirus (CMV) colitis is commonly seen in patients who are immunodeficient or have inflammatory bowel disease. Among the gastrointestinal sites affected by CMV, the colon is the most frequently affected, though rectal involvement is relatively rare. Reactivated CMV proctitis primarily occurs in [...] Read more.

Background: Cytomegalovirus (CMV) colitis is commonly seen in patients who are immunodeficient or have inflammatory bowel disease. Among the gastrointestinal sites affected by CMV, the colon is the most frequently affected, though rectal involvement is relatively rare. Reactivated CMV proctitis primarily occurs in elderly patients with comorbidities and is quite uncommon in immunocompetent individuals. Patients with reactivated CMV typically present with symptoms such as diarrhea, hematochezia, or tenesmus. Case presentation: We report a case of a female patient with uncontrolled diabetes who presented to the clinic complaining of perianal pain. She had no history of diarrhea or rectal bleeding. Lower GI endoscopy reported a small, localized, approximately 0.5 cm swelling in the proximal anal canal in addition to sigmoid diverticulosis. The biopsy revealed a small ulcer at the anorectal junction caused by CMV and confirmed by immunohistochemistry. Unfortunately, the patient was lost to follow-up before antiviral therapy could be initiated. Conclusions: This case highlights an uncommon presentation of reactivated CMV proctitis in an older diabetic patient presenting solely with perianal pain. Clinicians should maintain a high index of suspicion for CMV infection in elderly patients with comorbidities, even when classical colitis symptoms are absent, to avoid delayed diagnosis and management. Full article

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

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17 pages, 1065 KiB

Open AccessReview

Kyasanur Forest Disease Virus: Epidemiological Insights, Pathogenesis, Therapeutic Strategies, and Advances in Vaccines and Diagnostics

by Babita Bohra, Kumar Saurabh Srivastava, Ayush Raj, Nabanita Pal and Rahul Shukla

Viruses 2025, 17(8), 1022; https://doi.org/10.3390/v17081022 - 22 Jul 2025

Abstract

Kyasanur Forest disease virus (KFDV), a tick-borne Orthoflavivirus endemic to the Indian subcontinent, is a public health threat due to its recurrent outbreaks and expanding geographic range. This review provides a comprehensive overview of KFDV, encompassing its epidemiological trends, transmission dynamics, and ecological [...] Read more.

Kyasanur Forest disease virus (KFDV), a tick-borne Orthoflavivirus endemic to the Indian subcontinent, is a public health threat due to its recurrent outbreaks and expanding geographic range. This review provides a comprehensive overview of KFDV, encompassing its epidemiological trends, transmission dynamics, and ecological determinants that influence its spread. We delve into the current understanding of KFDV pathogenesis, highlighting key viral and host factors that drive infection and disease progression. Despite the absence of targeted antiviral therapies, recent advances have spurred the development of candidate therapeutics, including broad-spectrum antivirals and immunomodulators. We also discuss progress in vaccine development, with an emphasis on the limitations of the existing formalin-inactivated vaccine and the promise of next-generation platforms. Furthermore, we explore recent innovations in diagnostics, including molecular and serological tools, that aim to improve early detection and surveillance. A multidisciplinary approach integrating virology, immunology, ecology, and public health is essential for the effective management and eventual control of KFDV outbreaks. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Evolution, and Dispersion of Flaviviruses (2nd Edition))

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10 pages, 1491 KiB

Open AccessArticle

Development of a Point-of-Care Immunochromatographic Lateral Flow Strip Assay for the Detection of Nipah and Hendra Viruses

by Jianjun Jia, Wenjun Zhu, Guodong Liu, Sandra Diederich, Bradley Pickering, Logan Banadyga and Ming Yang

Viruses 2025, 17(7), 1021; https://doi.org/10.3390/v17071021 - 21 Jul 2025

Abstract

Nipah virus (NiV) and Hendra virus (HeV), which both belong to the genus henipavirus, are zoonotic pathogens that cause severe systemic, neurological, and/or respiratory disease in humans and a variety of mammals. Therefore, monitoring viral prevalence in natural reservoirs and rapidly diagnosing cases [...] Read more.

Nipah virus (NiV) and Hendra virus (HeV), which both belong to the genus henipavirus, are zoonotic pathogens that cause severe systemic, neurological, and/or respiratory disease in humans and a variety of mammals. Therefore, monitoring viral prevalence in natural reservoirs and rapidly diagnosing cases of henipavirus infection are critical to limiting the spread of these viruses. Current laboratory methods for detecting NiV and HeV include virus isolation, reverse transcription quantitative real-time PCR (RT-qPCR), and antigen detection via an enzyme-linked immunosorbent assay (ELISA), all of which require highly trained personnel and specialized equipment. Here, we describe the development of a point-of-care customized immunochromatographic lateral flow (ILF) assay that uses recombinant human ephrin B2 as a capture ligand on the test line and a NiV-specific monoclonal antibody (mAb) on the conjugate pad to detect NiV and HeV. The ILF assay detects NiV and HeV with a diagnostic specificity of 94.4% and has no cross-reactivity with other viruses. This rapid test may be suitable for field testing and in countries with limited laboratory resources. Full article

(This article belongs to the Section General Virology)

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22 pages, 3771 KiB

Open AccessArticle

Integrated Analysis of the 2022 SARS-CoV-2 Omicron Lineage Replacement Dynamics in Connecticut, US

by Nicholas F. G. Chen, Kien Pham, Chrispin Chaguza, Rafael Lopes, Fayette Klaassen, Chaney C. Kalinich, Yale SARS-CoV-2 Genomic Surveillance Initiative, Nicholas Kerantzas, Sameer Pandya, David Ferguson, Wade Schulz, Daniel M. Weinberger, Virginia E. Pitzer, Joshua L. Warren, Nathan D. Grubaugh and Anne M. Hahn

Viruses 2025, 17(7), 1020; https://doi.org/10.3390/v17071020 - 21 Jul 2025

Abstract

In 2022, consecutive sweeps of highly transmissible SARS-CoV-2 Omicron-derived lineages (B.1.1.529*) maintained viral transmission despite extensive antigen exposure from both vaccinations and infections. To better understand Omicron variant emergence in the context of the dynamic fitness landscape of 2022, we aimed to explore [...] Read more.

In 2022, consecutive sweeps of highly transmissible SARS-CoV-2 Omicron-derived lineages (B.1.1.529*) maintained viral transmission despite extensive antigen exposure from both vaccinations and infections. To better understand Omicron variant emergence in the context of the dynamic fitness landscape of 2022, we aimed to explore putative drivers behind SARS-CoV-2 lineage replacements. Variant fitness is determined through its ability to either outrun previously dominant lineages or more efficiently circumvent host immune responses to previous infections and vaccinations. By analyzing data collected through our local genomic surveillance program from Connecticut, USA, we compared emerging Omicron lineages’ growth rates, estimated infections, effective reproductive rates, average viral copy numbers, and likelihood for causing infections in recently vaccinated individuals. We find that newly emerging Omicron lineages outcompeted dominant lineages through a combination of enhanced viral shedding or advanced immune escape depending on the population-level exposure state. This analysis integrates individual-level sequencing data with demographic, vaccination, laboratory, and epidemiological data and provides further insights into host–pathogen dynamics beyond public aggregate data. Full article

(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)

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26 pages, 24138 KiB

Open AccessReview

Insights into the Landscape of Alphavirus Receptor and Antibody Interactions

by Shishir Poudyal, Abhishek Bandyopadhyay and Richard J. Kuhn

Viruses 2025, 17(7), 1019; https://doi.org/10.3390/v17071019 - 21 Jul 2025

Abstract

Alphaviruses engage a diverse array of attachment factors and receptors during viral entry, resulting in a broad host range and disease spectrum, and thus presenting them as a major global public health concern. The development of effective antivirals against these arboviruses relies on [...] Read more.

Alphaviruses engage a diverse array of attachment factors and receptors during viral entry, resulting in a broad host range and disease spectrum, and thus presenting them as a major global public health concern. The development of effective antivirals against these arboviruses relies on a comprehensive understanding of the molecular interplay between these viruses and host cell factors, as well as the wide range of immune responses that ensue following viral infection. In this review, we present the current understanding of the complex landscape of alphavirus interaction with attachment factors and entry receptors, some of which are characterized structurally, while others are characterized biochemically. Additionally, we provide an overview of the molecular bases of epitope recognition by neutralizing and non-neutralizing antibodies against alphaviruses, and how icosahedral symmetry influences these interactions, such as occupancy and neutralization potency. We further discuss the structural bases of epitope recognition of a few pan-alphavirus antibodies, their potential therapeutic implications, and offer future perspectives on the development of effective therapeutics against clinically relevant alphaviruses. Full article

(This article belongs to the Special Issue 15-Year Anniversary of Viruses)

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14 pages, 2669 KiB

Open AccessArticle

Glutamic Acid at Position 343 in PB2 Contributes to the Virulence of H1N1 Swine Influenza Virus in Mice

by Yanwen Wang, Qiu Zhong, Fei Meng, Zhang Cheng, Yijie Zhang, Zuchen Song, Yali Zhang, Zijian Feng, Yujia Zhai, Yan Chen, Chuanling Qiao and Huanliang Yang

Viruses 2025, 17(7), 1018; https://doi.org/10.3390/v17071018 - 20 Jul 2025

Abstract

The H1N1 swine influenza viruses CQ91 and CQ445, isolated from pigs in China, exhibited distinct virulence in mice despite sharing similar genomic constellations. CQ91 demonstrated higher pathogenicity (MLD₅₀: 5.4 log₁₀ EID₅₀) and replication efficiency in mice compared to [...] Read more.

The H1N1 swine influenza viruses CQ91 and CQ445, isolated from pigs in China, exhibited distinct virulence in mice despite sharing similar genomic constellations. CQ91 demonstrated higher pathogenicity (MLD₅₀: 5.4 log₁₀ EID₅₀) and replication efficiency in mice compared to CQ445 (MLD₅₀: 6.6 log₁₀ EID₅₀). Through reverse genetics, we found that the attenuation of CQ445 was due to a single substitution of glutamic acid (E) with lysine (K) at position 343 in the PB2 protein. Introducing the CQ445-PB2 (343K) into CQ91 significantly reduced viral replication and pathogenicity in mice, while replacing CQ445-PB2 with CQ91-PB2 (343E) restored virulence. In vitro studies showed that the K343E mutation impaired viral replication in MDCK and A549 cells and reduced polymerase activity in minigenome assays. Mechanistically, the amino acid at position 343 in the PB2 affects the transcription stage of the viral replication process. Structural modeling indicated that the charge reversal caused by E343K altered local electrostatic interactions without major conformational changes. Phylogenetic analysis revealed that PB2-343E is highly conserved (>99.9%) in human and swine H1/H3 influenza viruses, suggesting that PB2-343E confers an adaptive advantage. This study identifies PB2-343E as a critical determinant of influenza virus pathogenicity in mammals, highlighting its role in host adaptation. Full article

(This article belongs to the Section General Virology)

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20 pages, 1791 KiB

Open AccessReview

Regulation of Bombyx mori–BmNPV Protein Interactions: Study Strategies and Molecular Mechanisms

by Dan Guo, Bowen Liu, Mingxing Cui, Heying Qian and Gang Li

Viruses 2025, 17(7), 1017; https://doi.org/10.3390/v17071017 - 20 Jul 2025

Abstract

As a pivotal model organism in Lepidoptera research, the silkworm (Bombyx mori) holds significant importance in life science due to its economic value and biotechnological applications. Advancements in proteomics and bioinformatics have enabled substantial progress in characterizing the B. mori proteome. [...] Read more.

As a pivotal model organism in Lepidoptera research, the silkworm (Bombyx mori) holds significant importance in life science due to its economic value and biotechnological applications. Advancements in proteomics and bioinformatics have enabled substantial progress in characterizing the B. mori proteome. Systematic screening and identification of protein–protein interactions (PPIs) have progressively elucidated the molecular mechanisms governing key biological processes, including viral infection, immune regulation, and growth development. This review comprehensively summarizes traditional PPI detection techniques, such as yeast two-hybrid (Y2H) and immunoprecipitation (IP), alongside emerging methodologies such as mass spectrometry-based interactomics and artificial intelligence (AI)-driven PPI prediction. We critically analyze the strengths, limitations, and technological integration strategies for each approach, highlighting current field challenges. Furthermore, we elaborate on the molecular regulatory networks of Bombyx mori nucleopolyhedrovirus (BmNPV) from multiple perspectives: apoptosis and cell cycle regulation; viral protein invasion and trafficking; non-coding RNA-mediated modulation; metabolic reprogramming; and host immune evasion. These insights reveal the dynamic interplay between viral replication and host defense mechanisms. Collectively, this synthesis aims to provide a robust theoretical foundation and technical guidance for silkworm genetic improvement, infectious disease management, and the advancement of related biotechnological applications. Full article

(This article belongs to the Section Invertebrate Viruses)

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15 pages, 2357 KiB

Open AccessArticle

Development of a Novel, Highly Sensitive System for Evaluating Ebola Virus Particle Formation

by Wakako Furuyama, Miako Sakaguchi, Hanako Ariyoshi and Asuka Nanbo

Viruses 2025, 17(7), 1016; https://doi.org/10.3390/v17071016 - 19 Jul 2025

Abstract

Ebola virus (EBOV) causes severe hemorrhagic fevers in humans, and effective countermeasures remain limited. The EBOV-encoded major matrix protein VP40 is essential for viral assembly, budding, and particle release, making it a promising target for antiviral drug development. However, no approved drugs currently [...] Read more.

Ebola virus (EBOV) causes severe hemorrhagic fevers in humans, and effective countermeasures remain limited. The EBOV-encoded major matrix protein VP40 is essential for viral assembly, budding, and particle release, making it a promising target for antiviral drug development. However, no approved drugs currently target the viral particle formation process. In this study, we established a simple and highly sensitive screening system to evaluate VP40-mediated virus-like particle (VLP) formation under biosafety level −2 conditions. The system uses the HiBiT luminescence-based reporter fused to VP40, allowing for the detection of VP40 release. Our results demonstrate that the HiBiT sequence fused at the N-terminus [HiBiT-VP40 (N)] retains VP40′s ability to form VLPs, supporting its use as a functional reporter. Furthermore, we validated the system by assessing the role of Rab11-dependent trafficking in VP40-mediated budding and by evaluating the effect of nocodazole, a microtubule depolymerizer, on VLP release. This novel screening system provides a convenient and reliable platform for screening potential inhibitors targeting the late stages of EBOV infection, including viral particle formation and release. Additionally, its potential adaptability to other filoviruses suggests wide applicability in the discovery and development of additional novel therapeutic agents. Full article

(This article belongs to the Special Issue BSL4 Viruses: Understanding and Controlling Highly Infectious Pathogens)

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12 pages, 1625 KiB

Open AccessArticle

Rift Valley Fever Outbreak Investigation Associated with a Dairy Farm Abortion Storm, Mbarara District, Western Uganda, 2023

by Luke Nyakarahuka, Shannon Whitmer, Sophia Mulei, Joanita Mutesi, Jimmy Baluku, Jackson Kyondo, Amy Whitesell, Carson Telford, Alex Tumusiime, Calvin Richie Torach, Dianah Namanya, Mariam Nambuya, Dominic Muhereza, Zainah Kabami, Annet Nankya, David Muwanguzi, Francis Mugabi, Nelson Wandera, Rose Muhindo, Joel M. Montgomery, Julius J. Lutwama, Stephen Karabyo Balinandi, John D. Klena and Trevor R. Shoemaker Show full author list Hide full author list

Viruses 2025, 17(7), 1015; https://doi.org/10.3390/v17071015 - 19 Jul 2025

Abstract

In Africa, Rift Valley Fever poses a substantial risk to animal health, and human cases occur after contact with infected animals or their tissues. RVF has re-emerged in Uganda after nearly five decades, with multiple outbreaks recorded since 2016. We investigated a unique [...] Read more.

In Africa, Rift Valley Fever poses a substantial risk to animal health, and human cases occur after contact with infected animals or their tissues. RVF has re-emerged in Uganda after nearly five decades, with multiple outbreaks recorded since 2016. We investigated a unique RVF outbreak associated with an animal abortion storm of 30 events and human cases on a dairy farm in Mbarara District, Western Uganda, in February 2023. Genomic analysis was performed, comparing animal and human RVF viruses (RVFV) circulating in the region. A cluster of thirteen human RVF cases and nine PCR-positive animals could directly be linked with the abortion storm. Overall, during the year 2023, we confirmed 61 human RVFV cases across Uganda, 88.5% of which were reported to have had direct contact with livestock, and a high case fatality rate of 31%. We recommend implementing extensive health education programs in affected communities and using sustainable mosquito control strategies to limit transmission in livestock, coupled with initiating animal vaccination trials in Uganda. Full article

(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)

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