Viruses

17 pages, 1986 KB

Open AccessArticle

Next-Generation Sequencing Strategies During the 2024–2025 Avian Influenza A(H5N1) Emergency Response in the U.S

by Julia C. Frederick, Kristine A. Lacek, Matthew J. Wersebe, Bo Shu, Lisa M. Keong, Juliana DaSilva, Malania M. Wilson, Sydney R. Sheffield, Jimma Liddell, Natasha Burnett, Reina Chau, Amanda H. Sullivan, Yunho Jang, Juan A. De La Cruz, Elizabeth A. Pusch, Dan Cui, Yasuko Hatta, Sabrina Schatzman, Norman Hassell, Xiao-Yu Zheng, Ha T. Nguyen, Larisa Gubareva, Rebecca Kondor, Han Di, Vivien G. Dugan, Charles T. Davis, Benjamin L. Rambo-Martin and Marie K. Kirby Show full author list Hide full author list

Viruses 2026, 18(4), 482; https://doi.org/10.3390/v18040482 - 21 Apr 2026

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Abstract

The first influenza A(H5N1) human case associated with the A(H5N1) dairy cattle outbreak in the United States was identified in April 2024. The U.S. CDC response to this outbreak was activated days later and remained active until July 2025. During this time, 70 [...] Read more.

The first influenza A(H5N1) human case associated with the A(H5N1) dairy cattle outbreak in the United States was identified in April 2024. The U.S. CDC response to this outbreak was activated days later and remained active until July 2025. During this time, 70 human cases of influenza A(H5N1) were detected with a range of epidemiological links to sources of exposure. Next-generation sequencing (NGS) of human samples was an effectual mechanism for tracking and analyzing the outbreak evolution throughout the response. Due to the specimens’ importance and their variable physical quality, an assortment of laboratory methods was utilized including influenza segment-specific amplification, enrichment capture, short-read, and long-read sequencing. Combining these methods allowed for high-quality genomic data production with rapid turnaround times—typically 2 days from sample receipt to public database submission. By leveraging replicate sequencing, enrichment capture, and sequencing of diagnostic amplicons, valuable genomic data could be produced directly from human clinical specimens that would have normally been considered too weak for routine virologic surveillance sequencing. The resulting assemblies were characterized and analyzed by CDC and shared with local and state public health authorities to facilitate case investigations and risk assessment. These data were further used for phylogenetic analyses of viruses from human cases to investigate likely animal-to-human transmission events and identify clusters within the outbreak that might indicate trends in the types of exposures. Through the adaptable laboratory workflow and the rapid release of viral genomic data, the public health risk mitigation strategies could be evaluated and adjusted in real time. Full article

(This article belongs to the Special Issue H5N1 Influenza Viruses)

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16 pages, 5749 KB

Open AccessArticle

High-Throughput Sequencing Reveals Previously Undetected Viruses and Mixed Infections in Pepper (Capsicum annuum) in Hungary

by Emese Demián, Réka Sáray, Asztéria Almási, Kata Pogácsás and Katalin Salánki

Viruses 2026, 18(4), 481; https://doi.org/10.3390/v18040481 - 21 Apr 2026

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Abstract

The increasing global movement of plant material and the complexity of viral communities associated with cultivated crops complicate routine plant virus diagnostics. High-throughput sequencing (HTS) has therefore become an important tool for the comprehensive characterization of plant viromes. In this study, symptomatic pepper [...] Read more.

The increasing global movement of plant material and the complexity of viral communities associated with cultivated crops complicate routine plant virus diagnostics. High-throughput sequencing (HTS) has therefore become an important tool for the comprehensive characterization of plant viromes. In this study, symptomatic pepper (Capsicum annuum) samples submitted to our laboratory between 2020 and 2025 were investigated using HTS following unsuccessful routine diagnostic assays, despite the presence of virus-like symptoms. Virome analysis revealed the presence of multiple viruses with distinct biological characteristics. Eggplant mottled dwarf virus (EMDV) sequences were identified, representing, to our knowledge, the first sequence data from Hungary. In addition, sequences related to tobacco vein clearing virus (TVCV) showed highest similarity to endogenous viral element present in Capsicum annuum genome assemblies. Persistent viruses, including bell pepper alphaendornavirus (BPEV) and pepper cryptic virus 2 (PCV2), were also detected. These findings demonstrate the complex viral communities associated with cultivated pepper and highlight the limitations of strictly targeted diagnostic approaches. The results emphasize the value of HTS for comprehensive virome characterization in horticultural crops. Full article

(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World: 2nd Edition)

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20 pages, 2364 KB

Open AccessArticle

Testing Control Strategies for Foot-and-Mouth Disease in New England Using the InterSpread Plus Model: Impacts of Regional Zoning, Early Detection, and Enhanced Biosecurity

by Johnbosco U. Osuagwu, Julia M. Smith and Scott C. Merrill

Viruses 2026, 18(4), 480; https://doi.org/10.3390/v18040480 - 21 Apr 2026

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Abstract

Foot-and-mouth disease (FMD) poses a significant threat to the United States dairy industry. This study evaluates the effectiveness of regional zoning, enhanced detection, and biosecurity in controlling FMD spread, focusing on the New England milkshed, using the InterSpread Plus (ISP+) model. We adapted [...] Read more.

Foot-and-mouth disease (FMD) poses a significant threat to the United States dairy industry. This study evaluates the effectiveness of regional zoning, enhanced detection, and biosecurity in controlling FMD spread, focusing on the New England milkshed, using the InterSpread Plus (ISP+) model. We adapted a baseline ISP+ configuration incorporating United States dairy farm data, movement networks, cattle dealers, markets, and slaughterhouses, with milk processing plants as a model addition. Four hypotheses were tested to understand the impact of different biosecurity strategies: (H1) regional zoning limits the interregional spread of FMD post-detection; (H2) earlier detection in New England via increased passive surveillance reduces the overall outbreak impact; (H3) reduced indirect transmission through enhanced biosecurity measures improves FMD outbreak control; (H4) the combination of regional zoning and earlier detection provides synergistic reduction in FMD impact beyond either strategy alone. The four hypotheses were tested using three geographically distinct infection seed sets; 100 iterations of each scenario were simulated over 210 days and compared to the baseline. Key impact metrics included the daily number of infected premises, the outbreak duration, and the total number of infected premises across the outbreak scenarios. Results suggest shorter outbreak durations and reduced total infected premises under the hypothesized scenarios, compared to the baseline scenario. Kruskal–Wallis H tests confirmed significant differences across the baseline, regional zoning, early detection, enhanced biosecurity, and the combination of heightened passive surveillance with regional zoning scenarios in terms of total infected premises. Post hoc Dunn’s tests indicated that enhanced biosecurity outperformed other control strategies tested. These findings demonstrate that layered interventions may substantially curtail both the national amplification and local spread of FMD, and thus protect the consumer milk supply and reduce cascading economic shocks from an outbreak. Full article

(This article belongs to the Special Issue New Findings in Animal Biosecurity Related to Viral Diseases)

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10 pages, 850 KB

Open AccessArticle

Timing of Remdesivir Initiation and Clinical Outcomes in Hospitalized Patients with COVID-19 Who Are at High Risk of Disease Progression in Japan: A Health Insurance Claims Database Study

by Yuichiro Shindo, Yi Piao, Mark Berry, Heribert Ramroth and Manami Yoshida

Viruses 2026, 18(4), 479; https://doi.org/10.3390/v18040479 - 21 Apr 2026

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Abstract

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients [...] Read more.

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan. Full article

(This article belongs to the Special Issue Innovative Prophylactic and Therapeutics for the Treatment of Coronavirus Infection)

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21 pages, 1728 KB

Open AccessArticle

Active Participatory Surveillance for Early Detection of Notifiable Pathogens: A Case Study of the U.S. Swine Industry

by Berenice Munguía-Ramírez, Giovani Trevisan, Paul Morris, Gustavo S. Silva, Danyang Zhang, Chong Wang, Rodger Main and Jeffrey Zimmerman

Viruses 2026, 18(4), 478; https://doi.org/10.3390/v18040478 - 20 Apr 2026

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Abstract

The continued global spread of WOAH-listed pathogens via trade, transport, and travel calls for the implementation of biosecurity measures to protect the health of our national livestock industries, plus ongoing surveillance to verify that such measures are operative. Despite this urgency, surveillance must [...] Read more.

The continued global spread of WOAH-listed pathogens via trade, transport, and travel calls for the implementation of biosecurity measures to protect the health of our national livestock industries, plus ongoing surveillance to verify that such measures are operative. Despite this urgency, surveillance must be practical and affordable. Herein, we evaluated the performance and cost of participatory surveillance, a nontraditional surveillance design, using the U.S. swine industry as an example. In this context, “participatory” meant that herd veterinarians and/or producers collected and submitted samples from the herd to accredited laboratories for testing. To create an infected population (Phase 1), we simulated the introduction and spread of an unspecified notifiable pathogen within the 48 contiguous U.S states (66,637 swine farms, within 8,080,470 km²) using the USDA Animal Disease Spread Model software (v3.5.10.0). In Phase 2, we calculated the probability of detecting ≥1 infected farm as a function of producer participation, farm-level sensitivity, farm-level prevalence, and sampling frequency. The participatory design was effective: ≥90% probability of detecting the notifiable pathogen at 0.05% farm prevalence (33 positive farms among 66,637 farms) when farm-level sensitivity was ≥20% and producer participation was ≥40%. Depending on the specimen collected, the shipment method, and the test selected, costs ranged from $0.03 to $0.07 USD (€0.02 to €0.06) per pig in inventory. Thus, a surveillance design based on collecting and testing specimens from a few targeted pigs on each of many farms would be both affordable and effective at a national level. Full article

(This article belongs to the Special Issue ASFV Countermeasures, Pathogenesis, and Epidemiology)

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15 pages, 323 KB

Open AccessReview

Clinical and Pathophysiological Considerations Related to the Impact of Bulevirtide, a New Entry Inhibitor, in HBV-HDV Infection

by Raisa Eloise Barbu, Mariana Daniela Ignat, Roxana Elena Bogdan Goroftei, Alexia Anastasia Ștefania Baltă, Valerii Lutenco, Valentin Bulza, Valerian Ionuț Stoian, Simona Claudia Cambrea, Elena Dumea and Liliana Baroiu

Viruses 2026, 18(4), 477; https://doi.org/10.3390/v18040477 - 19 Apr 2026

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Abstract

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the [...] Read more.

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54–92% of patients and normalization of alanine transaminase (ALT) in 48.8–74% of patients after 23–144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance. Full article

(This article belongs to the Special Issue Hepatitis Viruses: Detection, Diagnosis and Treatment)

37 pages, 12756 KB

Open AccessReview

Advances in Antiviral Drug Development Targeting Enteroviruses: From Viral Proteins to Host Factors

by Jiaying Lu, Congyi Li, Wenzhe Cui, Yining Du, Jiayi Geng and Wenyan Zhang

Viruses 2026, 18(4), 476; https://doi.org/10.3390/v18040476 - 18 Apr 2026

Viewed by 1471

Abstract

Enteroviruses represent important human pathogens, posing a substantial disease burden, particularly in children under 5 years of age. Enteroviruses are the primary causative agents of hand-foot-and-mouth disease (HFMD) and are strongly associated with acute flaccid myelitis (AFM), with severe cases potentially resulting in [...] Read more.

Enteroviruses represent important human pathogens, posing a substantial disease burden, particularly in children under 5 years of age. Enteroviruses are the primary causative agents of hand-foot-and-mouth disease (HFMD) and are strongly associated with acute flaccid myelitis (AFM), with severe cases potentially resulting in significant neurological complications. Inactivated vaccines against EV-A71 based on the C4 genotype are currently available. However, there are no licensed direct antiviral agents for severe cases. By focusing on viral proteins and host factors, researchers have made great strides in the creation of antiviral medications that target enteroviruses. However, several viral candidates failed to progress in clinical development due to limited efficacy or side effects. This review discusses key findings in enterovirus antiviral research, analyzes the advantages and limitations of each drug target, and highlights knowledge gaps that need to be addressed to advance further development in this field. Full article

(This article belongs to the Special Issue Advances in Understanding Viral Pathogenesis and Host Immune Responses to Arboviruses and Respiratory Viruses)

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10 pages, 2411 KB

Open AccessArticle

Diagnostic and Phylogenetic Insights into a Human Rabies Virus Isolate from Romania

by Vlad Vuta, Maria Gradinaru, Mihnea Hurmuzache, Florica Bărbuceanu, Lenuta Zamfir, Răzvan Moțiu, Laura Schmid, Dirk Höper, Sten Calvelage, Thomas Müller and Conrad M. Freuling

Viruses 2026, 18(4), 475; https://doi.org/10.3390/v18040475 - 17 Apr 2026

Viewed by 615

Abstract

Rabies is a fatal zoonotic disease once clinical symptoms develop. In Europe, sustained animal rabies control programs have led to a marked decline in animal rabies and subsequently human rabies cases; however, sporadic infections continue to occur. In July 2025, a fatal case [...] Read more.

Rabies is a fatal zoonotic disease once clinical symptoms develop. In Europe, sustained animal rabies control programs have led to a marked decline in animal rabies and subsequently human rabies cases; however, sporadic infections continue to occur. In July 2025, a fatal case of autochthonous (locally acquired) human rabies was confirmed in Romania following a stray dog bite in a patient who did not receive post-exposure prophylaxis (PEP). Here, we report the first molecular characterization of a human rabies virus (RABV) strain isolated in Romania and place it in the context of contemporaneously circulating animal-derived RABV strains. Rabies virus infection was confirmed intra vitam by fluorescent antibody testing and both conventional and real-time RT-PCR on cerebrospinal fluid and saliva, with postmortem confirmation on skin and brain tissue. Whole-genome sequencing was performed on the human isolate and on 22 animal-derived RABV strains collected in northern Romania in 2025. Phylogenetic analyses revealed that all recent Romanian sequences clustered within the North-East European (NEE) rabies virus phylogenetic group and segregated into two geographically distinct genetic clusters: a north-western cluster, closely related to strains from Slovakia and Poland, and a larger north-eastern cluster, linked to viruses circulating in eastern Romania and the Republic of Moldova. The human-derived RABV genome was grouped within the north-eastern cluster and showed the highest genetic similarity to animal viral strains from the same geographical area, supporting a local transmission event. This demonstrates the importance of integrating human viral genomic data into the national rabies surveillance framework. Full article

(This article belongs to the Section Animal Viruses)

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30 pages, 5470 KB

Open AccessArticle

Investigation of the Viromes of Solanaceous Weeds in Hungary Using High-Throughput Sequencing Adds New Insights to Their Hidden Complexity

by Burim Ismajli, Zsuzsanna N. Galbács, Lilla Dorottya Péri, György Pasztor, András Péter Takács and Éva Várallyay

Viruses 2026, 18(4), 474; https://doi.org/10.3390/v18040474 - 17 Apr 2026

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Abstract

Weed control of solanaceous weeds growing with solanaceous crops is a constant challenge. Infected by viruses, they can also act as virus reservoirs, complicating this problem further. Viromes of annual Solanum nigrum, Datura stramonium, and Solanum dulcamara, a perennial climbing [...] Read more.

Weed control of solanaceous weeds growing with solanaceous crops is a constant challenge. Infected by viruses, they can also act as virus reservoirs, complicating this problem further. Viromes of annual Solanum nigrum, Datura stramonium, and Solanum dulcamara, a perennial climbing shrub, were investigated using RNA sequencing and validated using RT-PCR, revealing infection with nine viruses. Broad bean wilt virus 1 (BBWV1), cucumber mosaic virus (CMV), and potato virus M (PVM) were found to infect S. nigrum. Investigating only 46 plants revealed infection with Solanum dulcamara yellow fleck virus (SDYFV) not only in S. dulcamara but in a new host, D. stramonium, which also represents a new host of turnip yellows virus (TuYV). We described the first presence of a potato virus H (PVH)-like, and Oxybasis rubra mitovirus 1 (OxruMV1)-like virus in Europe, in S. dulcamara as a new host. Our results highlight the unexpected complexity of the viromes of solanaceous weeds, which should be considered during reliable and efficient plant protection strategies, in order to alleviate the virus reservoir role of the weeds. Full article

(This article belongs to the Special Issue Plant Viral Pathogens: Innovations in Detection, Genetic Diversity, and Evolutionary Dynamics)

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16 pages, 1092 KB

Open AccessReview

The Key Role of Complement Receptor CRIg in Kupffer Cell-Mediated Liver Disease Progression

by Xin-Zhou Sun and Yan Liu

Viruses 2026, 18(4), 473; https://doi.org/10.3390/v18040473 - 17 Apr 2026

Viewed by 635

Abstract

Liver diseases, ranging from chronic hepatitis and metabolic dysfunction to cirrhosis and hepatocellular carcinoma, represent a major global public health burden. As an immune-privileged organ, the liver harbors a unique and intricate immune microenvironment, which plays a dual role in pathogen clearance and [...] Read more.

Liver diseases, ranging from chronic hepatitis and metabolic dysfunction to cirrhosis and hepatocellular carcinoma, represent a major global public health burden. As an immune-privileged organ, the liver harbors a unique and intricate immune microenvironment, which plays a dual role in pathogen clearance and chronicity. Kupffer cells (KCs), the primary resident macrophages in the liver, constitute the first line of defense in liver innate immunity and play complex and important roles in pathogen recognition, phagocytosis, and the regulation of liver inflammation and immune responses. The complement receptor of the immunoglobulin superfamily (CRIg) is a membrane receptor that is specifically expressed on KCs. It serves not only as a sentinel for the liver against pathogen invasion but also as a sophisticated regulator for maintaining immune homeostasis. As a key component of the liver’s immune system, CRIg can efficiently mediate the clearance of complement-opsonized particles, thereby playing multidimensional roles in pathogen clearance, antigen cross-presentation, and the establishment of immune tolerance, functioning as both a “pathogen catcher” and an “immune brake.” This review focuses on the CRIg molecule, detailing its mechanisms in the recognition and phagocytic clearance by KCs, and its subsequent impact on hepatic immune responses. Furthermore, we explored the potential involvement of CRIg in the pathological progression of diverse liver diseases, including persistent inflammation, fibrosis, and hepatocarcinogenesis. This synthesis provides novel insights into the immunopathology of liver diseases and establishes a theoretical foundation for developing CRIg-targeted therapeutic strategies. Full article

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

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17 pages, 943 KB

Open AccessArticle

Immunogenicity and Safety of Biological E’s Monovalent rDNA Hepatitis B Vaccine (BEVAC^®) in Neonates and Infants: A Multicentre, Randomized, Phase IV Non-Inferiority Trial

by Subhash Thuluva, Subbareddy Gunneri, Siddalingaiah Ningaiah, Vijay Yerroju, Rammohan Reddy Mogulla, Chirag Dhar, Kamal Thammireddy, Raju Esanakarra, Pradeep Nanjappa and Niranjana S. Mahantshetti

Viruses 2026, 18(4), 472; https://doi.org/10.3390/v18040472 - 17 Apr 2026

Viewed by 799

Abstract

Biological E’s BEVAC^® is a recombinant DNA hepatitis B vaccine that has been used in India for more than a decade in routine early-life immunization and has recently been prequalified by the World Health Organization (WHO). This multicentre, single-blind, parallel-group, randomized phase [...] Read more.

Biological E’s BEVAC^® is a recombinant DNA hepatitis B vaccine that has been used in India for more than a decade in routine early-life immunization and has recently been prequalified by the World Health Organization (WHO). This multicentre, single-blind, parallel-group, randomized phase IV trial, conducted at seven study sites in India, compared the immunogenicity and safety of BEVAC^® with a licensed comparator vaccine (GeneVac-B^®, Serum Institute of India Pvt. Ltd, Pune, India.) in healthy term neonates and infants. Participants received three 0.5 mL doses administered intramuscularly at birth (within 24 h), 6 weeks of age, and 14 weeks of age. The primary endpoint was seroprotection (anti-HBs IgG ≥10 mIU/mL) at 28 days after the third dose (Day 126), compared using a non-inferiority margin of −10%. Secondary endpoints included safety and tolerability outcomes through Day 126. A total of 468 neonates were randomized (234 per group), of whom 44% were female. At Day 126, seroprotection rates were 98.2% (95% CI: 95.39, 99.50) with BEVAC^® and 99.1% (95% CI: 96.78, 99.89) with the comparator; the between-group difference was −0.9% (95% CI: −3.09, 1.24), meeting the prespecified non-inferiority criterion. Solicited adverse events within 7 days after any dose occurred in 29.1% (95% CI: 23.3, 35.3) of BEVAC^® recipients and 35.0% (95% CI: 28.9, 41.5) of comparator recipients, most commonly pyrexia, injection-site pain, and swelling; all were mild-to-moderate. No serious adverse events were reported. BEVAC^® demonstrated non-inferior immunogenicity to the licensed comparator and a comparable safety profile. Full article

(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics (2nd Edition))

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14 pages, 448 KB

Open AccessArticle

Development of a Multiplex PCR Method for Efficient Differential Diagnosis of Clinical Cases and Vaccine Immunization of Marek’s Disease

by Wen-Kai Zhang, Man Teng, Lu-Ping Zheng, Bin Shi, Wei-Dong Wang, Gui-Xi Li, Yong-Xu Zhao, Zhen Yang, Zu-Hua Yu and Jun Luo

Viruses 2026, 18(4), 471; https://doi.org/10.3390/v18040471 - 16 Apr 2026

Viewed by 664

Abstract

Marek’s disease (MD), caused by pathogenic Marek’s disease virus serotype 1 (MDV-1), is one of the most important avian immunosuppressive and neoplastic diseases and has led to huge economic losses to the poultry industry worldwide. Rapid and accurate clinical diagnosis is of great [...] Read more.

Marek’s disease (MD), caused by pathogenic Marek’s disease virus serotype 1 (MDV-1), is one of the most important avian immunosuppressive and neoplastic diseases and has led to huge economic losses to the poultry industry worldwide. Rapid and accurate clinical diagnosis is of great significance for efficient control of the disease. Herein, we have established a multiplex PCR (mPCR) method to simply differentiate all of the three types of MDV, using five specific primers targeting to MDV-1 oncogene meq or MDV-2 and MDV-3/HVT gB genes. Simultaneously, it can detect any type of virulent or vaccine MDV strains in one PCR reaction, with amplicons of the short (S) and long (L)-meq of MDV-1 strains, and the gB of MDV-2 and HVT vaccine strains. Non-specific amplifications of avian leukosis virus (ALV), reticuloendotheliosis virus (REV), or fowl adenovirus virus 4 (FAdV-4) were not observed, indicating a good specificity of this method. A total of 522 clinical samples of tumor-bearing or suspected diseased birds collected from 30 poultry farms were detected. The results demonstrated that the newly developed mPCR method accurately detected and differentiated epidemic MDV-1 infections and vaccine strains, and provided nearly 100% consistency for detecting clinical wild-type infections compared with conventional PCR amplification of the meq gene. Collectively, our data has provided a highly efficient method for early differential diagnosis of MD clinical cases, virus identification and future evaluation of vaccination efficacy in healthy chicken flocks, which would be meaningful for efficient control of the disease. Full article

(This article belongs to the Special Issue Avian Viruses and Antiviral Immunity)

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22 pages, 6523 KB

Open AccessArticle

SHAPE-MaP-Based Assessment of the Structure of Citrus Tristeza Virus Long Non-Coding RNA

by Arianna Spellman-Kruse, Jodi L. Bubenik, Tathiana Ferreira Sa Antunes, Alexander J. Lawrence, Maurice S. Swanson, Ying Wang and Svetlana Y. Folimonova

Viruses 2026, 18(4), 470; https://doi.org/10.3390/v18040470 - 16 Apr 2026

Viewed by 726

Abstract

The 5′-proximal region of the citrus tristeza virus (CTV) RNA genome is a hub where several elements involved in different facets of the virus cycle reside, including the sequences driving the production of the viral long non-coding RNA (lncRNA) LMT1. The sequence of [...] Read more.

The 5′-proximal region of the citrus tristeza virus (CTV) RNA genome is a hub where several elements involved in different facets of the virus cycle reside, including the sequences driving the production of the viral long non-coding RNA (lncRNA) LMT1. The sequence of this region is one of the most divergent genome areas, allowing for strain differentiation. Beyond its use in assessing viral population diversity, the region provides a valuable model for studying the conservation of RNA structure and function despite sequence variation. Here, we integrated comparative in silico analysis of the LMT1 region from variants of eight CTV strains with selective 2′-hydroxyl acylation, analyzed by primer extension and mutational profiling (SHAPE-MaP) probing of in vitro–generated LMT1 RNAs from two divergent strains, T36 and T68. The predicted consensus structures revealed 19 putative, conserved stem-loops. The SHAPE-MaP reactivity data supported and substantiated the thermodynamics-based predictions for the 15 previously uncharacterized stem-loops and two functional elements identified earlier. The strong structural conservation across strains highlights that the LMT1 RNA structure contributes to its function during CTV infection. These results provide the first experimentally supported structure of this viral lncRNA and lay the foundation for defining how individual RNA motifs influence CTV biology. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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22 pages, 674 KB

Open AccessArticle

Epidemiological Impact of Nirsevimab on Admissions for Bronchiolitis in a Pediatric Emergency Department: A Single-Center Cohort Study

by Emanuele Castagno, Carola Aschieri, Irene Ferri, Sara El Khbazi, Lorenzo Milani, Rosanna Irene Comoretto, Irene Raffaldi, Irene Tardivo, Marco Spada, Claudia Bondone and Franca Fagioli

Viruses 2026, 18(4), 469; https://doi.org/10.3390/v18040469 - 16 Apr 2026

Viewed by 902

Abstract

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in children < 24 months and a major public health concern, causing high rates of Emergency Department (ED) visits, hospitalizations, and Pediatric Intensive Care Unit (PICU) admissions. Nirsevimab is a recombinant monoclonal antibody [...] Read more.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in children < 24 months and a major public health concern, causing high rates of Emergency Department (ED) visits, hospitalizations, and Pediatric Intensive Care Unit (PICU) admissions. Nirsevimab is a recombinant monoclonal antibody recommended for all infants and high-risk children < 24 months. A retrospective single-center cohort study was conducted to evaluate the impact of nirsevimab introduction on bronchiolitis epidemiology in an Italian tertiary pediatric ED, accounting for 40,000 admissions/year. All children < 24 months who presented to our ED with bronchiolitis during two consecutive RSV seasons (first season: 1 October 2023 to 30 April 2024; second season: 1 October 2024 to 30 April 2025) were included. Descriptive and multivariate analyses are reported. Overall, 484 patients were analyzed (336 in 2023–2024; 148 in 2024–2025), with immunization coverage reaching 87.5% by April 2025. Compared with the previous season, RSV positivity decreased significantly (32.4% vs. 47.9%; p = 0.003) and was lower in immunized children (16.2% vs. 51.5%; p < 0.001). Immunization was associated with a reduced risk of RSV-positive swab in the second season (OR = 0.159, 95% CI: 0.059–0.397). Among RSV-negative patients, other respiratory viruses increased (p < 0.001), while co-infections increased in RSV-positive cases (p = 0.021). Hospitalization rates remained stable, though absolute admissions were halved. In conclusion, nirsevimab immunization reduced RSV burden, supporting its inclusion in universal prevention programs and the need for multicenter prospective studies to assess long-term outcomes. Full article

(This article belongs to the Special Issue RSV Epidemiological Surveillance: 3rd Edition)

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13 pages, 9823 KB

Open AccessArticle

Epidemiology, Genetic Evolution, and Capsid Protein Variation of Porcine Circovirus 2 in China (2023–2024): Sustained Dominance of Genotype PCV2d

by Ze Tong, Shiting Ni, Jiaqi Liu, Pingxuan Liu, Daisheng Shi, Guosheng Chen, Xin Zong, Yaning Lv, Renhang Xiao and Chen Tan

Viruses 2026, 18(4), 468; https://doi.org/10.3390/v18040468 - 15 Apr 2026

Viewed by 765

Abstract

Porcine circovirus type 2 (PCV2) is a pathogen of major importance in swine that is characterized by ongoing genetic evolution. To provide an updated epidemiological assessment for China, our study analyzed 1051 clinical samples collected from 27 provincial-level regions between 2023 and 2024. [...] Read more.

Porcine circovirus type 2 (PCV2) is a pathogen of major importance in swine that is characterized by ongoing genetic evolution. To provide an updated epidemiological assessment for China, our study analyzed 1051 clinical samples collected from 27 provincial-level regions between 2023 and 2024. The overall PCV2 positivity rate was 65.18%, with detection rates showing significant seasonal variation, with higher rates in spring and summer. Genotypic analysis of 379 open reading frame 2 (ORF2) sequences identified PCV2d as the dominant genotype (78.89%), and no significant geographic clustering was observed. Coinfection with porcine reproductive and respiratory syndrome virus (PRRSV) is common, yet statistical tests have revealed an epidemiologically independent relationship between the two viruses. Notably, analysis of the capsid (Cap) protein revealed that high-frequency amino acid mutations were concentrated in immunodominant loop regions. These mutations resulted in genotype-specific substitutions within key neutralizing epitopes. This study provides the latest large-scale national baseline data on PCV2 in China for 2023–2024. It systematically analyzes the epidemiological characteristics of the dominant PCV2d genotype in the post-African Swine Fever era, the patterns of antigenic epitope mutations in the Cap protein, and their potential impact on vaccine efficacy. The study fills a gap in recent national epidemiological data on PCV2 in China and provides a basis for the targeted prevention and control of PCV2 and the updating of vaccine strains. Full article

(This article belongs to the Special Issue Circoviruses in Domestic and Wild Animals)

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21 pages, 3110 KB

Open AccessArticle

Effect of Acid-Stabilizing Hemagglutinin Mutations on Immunogenicity and Heterologous Protection by H1N1 Influenza Virus mRNA-LNP Vaccines

by Chet R. Ojha, Samuel W. Rovito, Balaji Banoth, Hyunsuh Kim, Jeremy C. Jones, Mohamad-Gabriel Alameh, Po-Ling Chen, Richard J. Webby, Drew Weissman and Charles J. Russell

Viruses 2026, 18(4), 467; https://doi.org/10.3390/v18040467 - 15 Apr 2026

Viewed by 2257

Abstract

While current influenza vaccines often lack broad protection against antigenically drifted strains, some modified hemagglutinin (HA) protein antigens have shown promise in eliciting broadly neutralizing antibodies against conserved epitopes. During infection, the mildly acidic environment of the late endosome triggers irreversible HA conformational [...] Read more.

While current influenza vaccines often lack broad protection against antigenically drifted strains, some modified hemagglutinin (HA) protein antigens have shown promise in eliciting broadly neutralizing antibodies against conserved epitopes. During infection, the mildly acidic environment of the late endosome triggers irreversible HA conformational changes resulting in a post-fusion structure with altered antigenicity. While enhancing the stability of other structural class I viral fusion protein antigens has been instrumental in improving the effectiveness of COVID-19 and RSV vaccines, the role of HA stability in influenza vaccine immunogenicity is relatively unclear. Here, we used the nucleoside-modified mRNA-LNP platform to test engineered HA antigens with specific acid-stabilizing mutations (E47K, K58I, R106K, and K153E) in the HA stalk. All mutations increased HA acid stability, but E47K and R106K did not increase immunogenicity. K153E and K58I, but not E47K and R106K, enhanced the cell-surface expression of the HA protein in vitro. In mice, K153E- and K58I-containing mRNA-LNP vaccines elicited increased neutralizing antibody titers against homologous virus. K153E conferred greater protection than wild-type vaccine against lethal heterologous A/PR/8/34 challenge at low doses (0.5–1.0 µg), despite the absence of neutralizing antibodies against the challenge strain. K153E also elicited greater expansion of antigen-specific antibody-secreting cells (ASCs) in the bone marrow, as well as cross-reactive T follicular helper (Tfh) cells in the spleen. For the vaccines studied, increased HA expression was a stronger correlate of mRNA-LNP enhancement than increased HA stability. Full article

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

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19 pages, 6774 KB

Open AccessArticle

TRIM13 Positively Regulates the NF-κB Signaling Pathway Induced by Encephalomyocarditis Virus

by Xiaolan Ji, Donglin Bi, Mingqi Liu, Xiangru Du, Zhiqi Wang, Haiqing Li, Jinluan Wang, Yiyang Fan, Hao Gao, Derong Zhang, Jialin Bai and Qiongyi Li

Viruses 2026, 18(4), 466; https://doi.org/10.3390/v18040466 - 14 Apr 2026

Viewed by 459

Abstract

Encephalomyocarditis virus (EMCV) belongs to the genus Cardiovirus of the family Picornaviridae. It is a non-enveloped, positive-sense, single-stranded RNA virus and an important pathogen causing encephalomyocarditis (EMC). Tripartite motif 13 (TRIM13) is a member of the tripartite motif (TRIM) family and serves as [...] Read more.

Encephalomyocarditis virus (EMCV) belongs to the genus Cardiovirus of the family Picornaviridae. It is a non-enveloped, positive-sense, single-stranded RNA virus and an important pathogen causing encephalomyocarditis (EMC). Tripartite motif 13 (TRIM13) is a member of the tripartite motif (TRIM) family and serves as an important effector molecule in antiviral innate immunity. However, its antiviral activity and underlying molecular mechanisms during EMCV infection remain unknown. In this study, we identified TRIM13 as a regulator of NF-κB activation. TRIM13, dependent on its E3 ubiquitin ligase activity, directly binds to IκBα and dose-dependently increases its phosphorylation level. To determine the chain type of IκBα polyubiquitination, antibodies specific for K48-linked and K63-linked ubiquitin were used. Our data indicated that IκBα was subjected to polyubiquitination independent of K48 and K63 linkages. This interaction promotes non-K48/K63-linked polyubiquitination of IκBα, thereby inducing NF-κB nuclear translocation. Subsequently, nuclear NF-κB activates the secretion of pro-inflammatory cytokines, exacerbating inflammatory responses and ultimately facilitating EMCV infection. Full article

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

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17 pages, 4426 KB

Open AccessArticle

Plasma ACE and ACE2 Levels Are Altered in Patients with COVID-19

by Murat Oz, Wassim Chehadeh, Omamah Alfarisi and Farhan S. Cyprian

Viruses 2026, 18(4), 465; https://doi.org/10.3390/v18040465 - 14 Apr 2026

Viewed by 576

Abstract

Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin–angiotensin system (RAS) in COVID-19 [...] Read more.

Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin–angiotensin system (RAS) in COVID-19 pathophysiology. Measurement of circulating RAS components, including ACE and ACE2, may therefore provide an insight into disease severity and underlying mechanisms. Subjects and Methods: In this retrospective cohort study, 224 adults with PCR-confirmed COVID-19 were stratified by World Health Organization disease-severity criteria into asymptomatic, mild, mild-pneumonia, severe, and critical groups. Plasma ACE and ACE2 concentrations were quantified by ELISA. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results and Conclusions: Increasing disease severity was associated with higher mortality, elevated body mass index, and higher viral load estimates. Severe and critical illness was characterized by leukocytosis with neutrophilia, marked lymphopenia, anemia, elevated inflammatory and coagulation markers, renal dysfunction, and hypoalbuminemia. Plasma ACE2 levels declined progressively with increasing severity and were significantly lower in patients with mild-pneumonia, severe, or critical illness compared with asymptomatic or mild cases, showing a strong inverse correlation with severity. In contrast, plasma ACE levels increased significantly with disease severity. The resulting increase in the ACE/ACE2 ratio indicates a progressive shift toward the pro-inflammatory arm of the RAS, providing mechanistic insight into the COVID-19 pathophysiology. Full article

(This article belongs to the Section Coronaviruses)

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33 pages, 1033 KB

Open AccessConference Report

25th Annual Meeting of the Rocky Mountain Virology Association

by Talia J. Byrne-Haber, Kylee N. Pham, Arianna Joob, Samantha M. Pinto, Oshani C. Ratnayake, Ryan Thompson, Joel Rovnak and Rushika Perera

Viruses 2026, 18(4), 464; https://doi.org/10.3390/v18040464 - 14 Apr 2026

Viewed by 788

Abstract

Located on the traditional and ancestral homelands of the Arapaho, Cheyenne, and Ute Nations, Colorado State University’s Mountain Campus hosted the 25th Annual Rocky Mountain Virology Association meeting. The three-day event, held from 26 September to 28 September 2025, welcomed 152 participants focused [...] Read more.

Located on the traditional and ancestral homelands of the Arapaho, Cheyenne, and Ute Nations, Colorado State University’s Mountain Campus hosted the 25th Annual Rocky Mountain Virology Association meeting. The three-day event, held from 26 September to 28 September 2025, welcomed 152 participants focused on the following topics: viruses, prions, immunology, transmission, structural biology, and vector biology. This year’s Randall Jay Cohrs Keynote Presentation summarized ongoing research on viral glycoproteins in relation to viral entry and assembly. Understanding the role of viral glycoproteins is essential in vaccine and antiviral development for enveloped RNA viruses. Alongside rigorous scientific discourse and networking, attendees made the most of their time by hiking amidst beautiful fall colors, wildlife, and young aspens starting the forest anew. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations from the 25th annual meeting. Full article

(This article belongs to the Section General Virology)

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17 pages, 3109 KB

Open AccessReview

Roles of the Chemokine Receptor CX3CR1 in the Pathogenesis of RSV Infections

by Robert Meineke, Martin Ludlow, Albert D. M. E. Osterhaus and Guus F. Rimmelzwaan

Viruses 2026, 18(4), 463; https://doi.org/10.3390/v18040463 - 13 Apr 2026

Viewed by 981

Abstract

CX3CR1 is a chemokine receptor expressed on respiratory epithelial and immune cells and has been identified as a host factor important for infections with respiratory syncytial virus (RSV). In this review, we discuss the roles CX3CR1 plays in the pathogenesis of RSV infections [...] Read more.

CX3CR1 is a chemokine receptor expressed on respiratory epithelial and immune cells and has been identified as a host factor important for infections with respiratory syncytial virus (RSV). In this review, we discuss the roles CX3CR1 plays in the pathogenesis of RSV infections as a viral entry receptor and regulator of immune cell trafficking. The conserved CX3C motif of the RSV G glycoprotein binds to CX3CR1 to mediate viral attachment and entry into respiratory epithelial cells. Furthermore, soluble G protein (sG) can bind to CX3CR1 and competitively interfere with cell signaling induced by the chemokine CX3CL1, resulting in inhibition of immune cell recruitment to the site of infection. In addition, sG engages TLR2 on epithelial cells, activating MyD88-NF-κB signaling and priming the NLRP3 inflammasome, which enhances viral dissemination through pyroptotic cell death. CX3CR1 signaling should be viewed as one of several overlapping host factors that—along with developmental changes in interferon and STAT3 signaling, airway anatomy, inflammasome activity, and tissue-resident memory responses—contribute to differential disease outcomes of RSV infection. A more complete molecular understanding of RSV-CX3CR1 interactions and downstream host responses may enable the development of improved prevention and treatment strategies. Full article

(This article belongs to the Special Issue Respiratory Syncytial Virus: Pathogenesis, Prevention and Treatment)

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17 pages, 2294 KB

Open AccessArticle

In Vitro Antiviral Properties of Two Recombinant Sendai Virus Vectors Encoding ORFV 011 and ORFV 059 Genes

by Álex Gómez, Idoia Glaria, Irati Moncayola, Leonor Puzol, Laura Arriazu, Ainhoa Calero, Ignacio de Blas, Mikel Nazábal, Itziar Hualde, Benhur Lee, Lluís Luján, Ralf Amann, Irache Echeverría and Ramsés Reina

Viruses 2026, 18(4), 462; https://doi.org/10.3390/v18040462 - 13 Apr 2026

Viewed by 886

Abstract

Orf virus (ORFV) is a globally distributed zoonotic parapoxvirus that causes a highly contagious mucocutaneous disease in small ruminants. Despite the urgent demand for vaccination-based control, no licensed vaccines are currently available universally. In this study, we generated two recombinant Sendai virus (SeV) [...] Read more.

Orf virus (ORFV) is a globally distributed zoonotic parapoxvirus that causes a highly contagious mucocutaneous disease in small ruminants. Despite the urgent demand for vaccination-based control, no licensed vaccines are currently available universally. In this study, we generated two recombinant Sendai virus (SeV) vectors expressing ORFV 011 (rSeV-GFP-B2L) and ORFV 059 (rSeV-GFP-059) genes and evaluated their ability to stimulate antiviral responses in vitro. Following the transduction, we assessed transgene expression, innate immune activation, induction of interferon-stimulated genes (A3Z1, OBST2, SAMHD1), and antiviral activity. Both vectors significantly upregulated pattern recognition receptors (TLRs, RIG-I) and type I interferon (IFN-β) genes, with rSeV-GFP-059 inducing the strongest response. Remarkably, OBST2 was robustly upregulated, suggesting a potential role in restricting ORFV replication. Antiviral activity assays revealed a marked reduction in ORFV DNA copies and a mild decrease in ORFV RNA transcription in rSeV-GFP-059-transduced cells, particularly at later time points, accompanied by complete abrogation of the typical cytopathic effect. Collectively, these results demonstrate that SeV-based vectors, particularly rSeV-GFP-059, efficiently prime antiviral immunity and suppress ORFV replication, establishing a promising platform for further in vivo vaccine evaluation in sheep. Full article

(This article belongs to the Special Issue Viral Diseases of Sheep and Goats)

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37 pages, 1436 KB

Open AccessReview

Oncolytic Virotherapy and Immunogenic Cell Death: Mechanisms, Platforms, and Clinical Translation

by Hiroyuki Inoue

Viruses 2026, 18(4), 461; https://doi.org/10.3390/v18040461 - 13 Apr 2026

Cited by 1 | Viewed by 1586

Abstract

Oncolytic viruses represent a paradigm-shifting approach to cancer immunotherapy, functioning as in situ vaccines that convert immunologically “cold” tumors into “hot” tumors through induction of immunogenic cell death (ICD). Despite the clinical success of checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed [...] Read more.

Oncolytic viruses represent a paradigm-shifting approach to cancer immunotherapy, functioning as in situ vaccines that convert immunologically “cold” tumors into “hot” tumors through induction of immunogenic cell death (ICD). Despite the clinical success of checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), many patients exhibit primary or acquired resistance due to insufficient tumor immunogenicity and exclusion of tumor-infiltrating lymphocytes. Oncolytic viruses address this limitation by selectively replicating in tumor cells, inducing robust ICD characterized by four cardinal hallmarks: calreticulin exposure, ATP secretion, HMGB1 release, and type I interferon production. This review systematically examines the molecular mechanisms underlying virus-induced ICD, compares DNA virus platforms (Vaccinia, HSV-1, Adenovirus) with RNA virus platforms (Coxsackieviruses A21, A11, and B3), and analyzes clinical trial data demonstrating synergistic efficacy when combined with checkpoint inhibitors. Notably, RNA viruses generate higher type I interferon responses compared to DNA viruses, correlating with superior clinical outcomes. Coxsackievirus A21 combined with pembrolizumab achieved a 47% objective response rate in melanoma in the CAPRA trial, representing notable efficacy exceeding either monotherapy. Coxsackievirus A11 demonstrates exceptional selectivity for thoracic cancers through ICAM-1-dependent receptor tropism and potent immunogenic cell death induction. Japanese researchers have pioneered microRNA-targeted Coxsackievirus B3, achieving cardiac safety attenuation while preserving complete oncolytic potency and ICD-inducing capacity. This comprehensive analysis synthesizes molecular mechanisms, platform comparisons, clinical efficacy data, and translational challenges to guide future development of oncolytic virotherapy as a cornerstone of cancer immunotherapy. Full article

(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy 2025–2026)

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22 pages, 12280 KB

Open AccessArticle

Sorting Nexin 10 Mediates Endosomal Acidification and Autophagy to Promote Influenza A Virus Infection

by Lizhu Chen, Haobin Li, Huiyi Guo, Jinlong Liang, Yingyuan Zhong, Xucheng He, Wenjiao Wu and Shuwen Liu

Viruses 2026, 18(4), 460; https://doi.org/10.3390/v18040460 - 12 Apr 2026

Viewed by 723

Abstract

The infection cycle of the Influenza A Virus (IAV) typically requires host factors to regulate replication and proliferation. However, the roles of these factors remain undiscovered. This study focuses on Sorting Nexin 10 (SNX10), which is involved in regulating membrane trafficking and endosomal [...] Read more.

The infection cycle of the Influenza A Virus (IAV) typically requires host factors to regulate replication and proliferation. However, the roles of these factors remain undiscovered. This study focuses on Sorting Nexin 10 (SNX10), which is involved in regulating membrane trafficking and endosomal stabilization. Our previous study identified that SNX10 facilitates the replication of human coronavirus OC43 through enhancing clathrin-mediated endocytosis. In our present study, we found that SNX10 significantly promoted IAV infection in host cells. The conditional knockout of Snx10 in mice lungs prolonged survival following IAV challenge. Mechanistically, SNX10 facilitated the production of acidic endosomal vesicles and promoted the accumulation of pro-viral autophagic structures, a process supported by the specific interaction between SNX10 and the viral NP and M2 protein of IAV. Blocking SNX10-mediated acidic endosomal vesicles and autophagosome formation demonstrated antiviral effects. Moreover, IAV infection increased SNX10 protein levels by suppressing its ubiquitination, suggesting that SNX10 could serve as a potential host-derived antiviral drug target. Full article

(This article belongs to the Special Issue Interplay Between Influenza Virus and Host Factors, 2nd Edition)

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15 pages, 1351 KB

Open AccessArticle

A Mouse-Adapted CHIKV Strain Harboring E2-K200R and Non-Structural Mutations Exhibits Enhanced Pathogenicity in Multiple Rodent Models

by Cong Tang, Bai Li, Qing Huang, Yun Yang, Wenhai Yu, Yanan Zhou, Daoju Wu, Hao Yang, Haixuan Wang, Junbin Wang and Shuaiyao Lu

Viruses 2026, 18(4), 459; https://doi.org/10.3390/v18040459 - 12 Apr 2026

Viewed by 702

Abstract

Chikungunya virus (CHIKV) pathogenesis research has long been constrained by the lack of suitable immunocompetent rodent models. Through serial passaging in A129 and C57BL/6 mice, we obtained an adapted strain (CHIKV-Adapt) harboring an E2-K200R substitution along with non-structural protein mutations. Phenotypic analysis in [...] Read more.

Chikungunya virus (CHIKV) pathogenesis research has long been constrained by the lack of suitable immunocompetent rodent models. Through serial passaging in A129 and C57BL/6 mice, we obtained an adapted strain (CHIKV-Adapt) harboring an E2-K200R substitution along with non-structural protein mutations. Phenotypic analysis in C57BL/6 mice, BALB/c mice, and hamster models demonstrated that compared to the wild-type virus CHIKV-Adapt induced significantly higher and more prolonged viremia, broader tissue tropism, and more severe internal joint inflammation, without exacerbating external swelling. Notably, the K200R mutation did not alter the viral replication kinetics in vitro and was predicted not to affect its binding pattern to the MXRA8 receptor. Furthermore, mice challenged 160 days after primary infection exhibited nearly complete protective immunity. These findings indicate that E2-K200R is a critical adaptive mutation that, together with accompanying non-structural mutations, significantly enhances CHIKV replication capacity and pathogenicity in immunocompetent rodents without changing its in vitro replication ability or predicted receptor-binding mode. The acquisition of this adapted strain provides a new tool for CHIKV pathogenesis research and vaccine evaluation. Full article

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

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29 pages, 3848 KB

Open AccessReview

Integrative Insights into the Immunopathogenesis and Organ-Specific Immunological Mechanisms of Long COVID: A Narrative Review

by Supriya Mahajan, Saurabh Mahajan and Nidhi Kaushik

Viruses 2026, 18(4), 458; https://doi.org/10.3390/v18040458 - 10 Apr 2026

Viewed by 1521

Abstract

Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum [...] Read more.

Long COVID (LC), also referred to as post-acute sequelae of SARS-CoV-2 infection, is characterized by persistent symptoms originating 3 months following acute COVID-19, lasting for at least two months and frequently affecting individuals who initially experienced mild to moderate disease. The clinical spectrum is heterogeneous, involving respiratory, cardiovascular, neurological, renal, gastrointestinal, and endocrine systems, thereby posing substantial diagnostic and therapeutic challenges. Despite extensive investigation, the precise immunopathogenic mechanisms underlying LC remain incompletely defined. Accumulating evidence suggests that LC is driven by a multifactorial interplay of persistent viral antigen reservoirs, chronic immune activation, dysregulated innate and adaptive immune responses, autoimmunity, endothelial dysfunction, microvascular injury, and aberrant tissue repair. These systemic immune perturbations manifest variably across different organs, contributing to the diverse clinical phenotypes observed. However, mechanistic clarity is hindered by heterogeneity in study designs, limited longitudinal data, and the absence of standardized immunological profiling. This narrative review provides integrative insights into the immunopathogenesis of LC, synthesizing current evidence on systemic immune dysregulation and organ-specific immunological mechanisms. A conceptual framework is proposed to facilitate a structured understanding of this complex syndrome and to guide future research toward targeted immunomodulatory strategies. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 4th Edition)

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8 pages, 682 KB

Open AccessCommentary

Viruses in Extreme Marine Environments and Their Potential Existence in Extraterrestrial Environments

by Andrew McMinn, Yantao Liang, Ziyue Wang and Min Wang

Viruses 2026, 18(4), 457; https://doi.org/10.3390/v18040457 - 10 Apr 2026

Viewed by 883

Abstract

Viruses are abundant and widespread in extreme marine environments, such as sea ice, hydrothermal vents, and ocean trenches. They occur at temperatures up to 122 °C and down to −30 °C and pressures exceeding 100 MPa. Their distribution in these environments is closely [...] Read more.

Viruses are abundant and widespread in extreme marine environments, such as sea ice, hydrothermal vents, and ocean trenches. They occur at temperatures up to 122 °C and down to −30 °C and pressures exceeding 100 MPa. Their distribution in these environments is closely correlated with that of their extremophile hosts, which are mostly bacteria, archaea, and microeukaryotes. Viruses have been shown to be capable of long-term survival in conditions simulating interstellar conditions. However, for them to reproduce, they would still need a host. Many recent astro-biological investigations have focused on habitability, specifically the ability of a planet to support the activity of at least one lifeform. The most likely candidates for extraterrestrial habitability in our solar system are the sea ice moons of Jupiter and Saturn, namely Europa and Enceladus. These are both thought to contain subsurface oceans of liquid water and potentially access to the necessary elements for microbial growth. If microorganisms were to be detected in these extraterrestrial environments, viruses might also be found coexisting with their host cells. Full article

(This article belongs to the Special Issue Viruses in Extreme Environments)

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15 pages, 862 KB

Open AccessReview

Molecular Mimics: How Viral Genomes Dupe Their Host by Usurping CTCF to Establish Infection

by Clairine I. S. Larsen, Rhiannon R. Abrahams and Kinjal Majumder

Viruses 2026, 18(4), 456; https://doi.org/10.3390/v18040456 - 10 Apr 2026

Viewed by 988

Abstract

The eukaryotic genome is organized into distinct structural units dictated by architectural proteins. The major host architectural protein CCCTC-binding factor (CTCF) is usurped by DNA viruses to regulate viral gene expression. This review will discuss the major ways large (EBV, HSV, HCMV) and [...] Read more.

The eukaryotic genome is organized into distinct structural units dictated by architectural proteins. The major host architectural protein CCCTC-binding factor (CTCF) is usurped by DNA viruses to regulate viral gene expression. This review will discuss the major ways large (EBV, HSV, HCMV) and small (HPV, HBV, AAV) DNA viruses mimic eukaryotic genome topology using CTCF to regulate viral gene expression. We will further discuss how changes in genome topology can drive virally induced oncogenic progression. Knowledge gained from studying viral genome folding mechanisms will inform the development of targeted anti-viral agents and inform the modification of viruses to serve as gene therapy vectors. Full article

(This article belongs to the Special Issue Nuclear Architecture in Viral Infection)

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14 pages, 273 KB

Open AccessArticle

Association of Oral Papivir/Pavirona^® Supplementation with HPV DNA Clearance

by Betul Gungor Serin, Bilal Esat Temiz, Haticegul Tuncer, Muhammed Onur Atakul, Ali Can Gunes, Taylan Onat, Utku Akgor, Derman Basaran, Zafer Selcuk Tuncer and Murat Gultekin

Viruses 2026, 18(4), 455; https://doi.org/10.3390/v18040455 - 9 Apr 2026

Viewed by 1012

Abstract

Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a [...] Read more.

Background: Persistent cervical human papillomavirus (Human papillomavirus) infection remains a significant public health concern, as it is the primary etiological factor in the development of cervical cancer and its precursor lesions. While prophylactic vaccination and standard screening programs are cornerstones of prevention, a substantial proportion of women with established infection are managed conservatively, often with prolonged follow-up and associated psychological burden. Interest has therefore grown in supportive interventions that may facilitate viral clearance during routine clinical management. Methods: This retrospective cohort study included 239 women with confirmed cervical Human papillomavirus infection followed at a tertiary referral center between February 2023 and August 2025. Participants were classified into a treatment group receiving oral Papivir/Pavirona^® twice daily for six months (n = 119) and a control group managed with routine clinical follow-up alone (n = 120). Human papillomavirus DNA testing and cervical cytology were evaluated at baseline and at 6 and 12 months. Results: Human papillomavirus clearance rates were significantly higher in the Papivir/Pavirona^® group compared with controls at both 6 and 12 months. Cytological regression was also more frequent in the treatment group at both time points. In multivariate logistic regression analysis, Papivir/Pavirona^® use emerged as the only independent predictor of both Human papillomavirus clearance and cytological regression, while demographic, reproductive, behavioral, and virological baseline characteristics were not significantly associated with outcomes. Conclusions: Papivir/Pavirona^® supplementation was associated with increased Human papillomavirus clearance and cytological regression rates in women with cervical Human papillomavirus infection, suggesting a potential supportive role alongside standard clinical follow-up. Full article

18 pages, 3638 KB

Open AccessArticle

Glycyrrhizic Acid-Modified Gold Nanoparticles Show Inhibitory Activity Against PRRSV and SARS-CoV-2 Pseudovirus In Vitro

by Ting Tong, Xiaotong Zhang, Yating Lei, Linjie Li, Shaobo Xiao and Jiangong Liang

Viruses 2026, 18(4), 454; https://doi.org/10.3390/v18040454 - 9 Apr 2026

Viewed by 691

Abstract

The development of novel antiviral nanomaterials is an important approach for addressing emerging viral threats. In this study, glycyrrhizic acid-modified gold nanoparticles (GA-Au NPs) were successfully synthesized and characterized, and their inhibitory effects against porcine reproductive and respiratory syndrome virus (PRRSV) and severe [...] Read more.

The development of novel antiviral nanomaterials is an important approach for addressing emerging viral threats. In this study, glycyrrhizic acid-modified gold nanoparticles (GA-Au NPs) were successfully synthesized and characterized, and their inhibitory effects against porcine reproductive and respiratory syndrome virus (PRRSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus were systematically evaluated. At non-cytotoxic concentrations, GA-Au NPs showed inhibitory activity against PRRSV in vitro. Stage-specific assays suggested that intracellular replication-related events were prominently affected, with additional inhibitory effects observed during adsorption, invasion, and release, whereas no direct virucidal activity was detected under the tested conditions. Furthermore, GA-Au NPs dose-dependently reduced SARS-CoV-2 pseudovirus infection-associated reporter signals in HEK-293T-ACE2 cells, supporting inhibitory activity in an additional viral model. In conclusion, GA-Au NPs represent a biocompatible antiviral nanomaterial with multi-stage inhibitory activity against PRRSV and inhibitory effects in a SARS-CoV-2 pseudovirus model, supporting their further evaluation as antiviral nanomaterials in enveloped virus-related models. Full article

(This article belongs to the Special Issue Veterinary Virology and One Health)

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13 pages, 1106 KB

Open AccessCommentary

Mpox (Monkeypox) in Pregnant Women, the Placenta and Fetus: Correlation with Maternal-Fetal Transmission, Pathology and Strain Differences from MPXV Clades Ia, Ib, IIa, and IIb

by David A. Schwartz

Viruses 2026, 18(4), 453; https://doi.org/10.3390/v18040453 - 9 Apr 2026

Viewed by 833

Abstract

Since the elimination of smallpox, mpox (monkeypox) is the most medically significant orthopoxvirus infection. As a result of numerous regional, national and global outbreaks of MPXV (mpox virus), there is an abundance of new data available on the effects of the different viral [...] Read more.

Since the elimination of smallpox, mpox (monkeypox) is the most medically significant orthopoxvirus infection. As a result of numerous regional, national and global outbreaks of MPXV (mpox virus), there is an abundance of new data available on the effects of the different viral clades on clinical obstetrical and perinatal outcomes when infection occurs in pregnancy. In addition, there have been additional placentas from cases of congenital MPXV infection available for study. These recent data indicate that there are prominent differences between viral strains and their effects on the fetus, with MPXV Clade I strains (Ia, Ib) having the greatest risk for an adverse outcome in pregnancy, and Clade II strains (IIa, IIb) having far less risk. In particular, the ongoing outbreak of MPXV Clade Ib in the DRC indicates that there is a significant risk for adverse perinatal outcomes associated with infection in pregnancy, especially during the first trimester. These outcomes include spontaneous abortion, stillbirth, neonatal death and congenital mpox. The placenta in cases of congenital infection demonstrates abundant virus in the chorionic villi, with prominent involvement of Hofbauer cells. Similar to smallpox, transplacental transmission and adverse pregnancy outcomes are an important feature of certain strains of this orthopoxvirus infection when occurring in pregnant women. Full article

(This article belongs to the Special Issue Mpox (Monkeypox): From Neglected Tropical Disease to Emerging Global Pathogen)

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