Viruses

10 pages, 744 KB

Open AccessCase Report

Epstein–Barr Virus-Positive Primary CNS Lymphoma in a Patient Receiving Mycophenolate Mofetil: Diagnostic and Therapeutic Considerations

by Danielle N. Burner, Giselle Y. López, Justin T. Low and Micah A. Luftig

Viruses 2026, 18(5), 485; https://doi.org/10.3390/v18050485 (registering DOI) - 22 Apr 2026

Abstract

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving [...] Read more.

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non–germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes. Full article

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

13 pages, 3124 KB

Open AccessArticle

Targeted and Effective Phage-Based Biocontrol of Black Rot Disease in Broccoli

by Miloud Sabri, Khaoula Mektoubi, Orges Cara, Roukia Bougheloum, Angelo De Stradis, Giuseppe Parrella and Toufic Elbeaino

Viruses 2026, 18(5), 484; https://doi.org/10.3390/v18050484 - 22 Apr 2026

Abstract

Xanthomonas species are Gram-negative bacterial pathogens responsible for diseases in over 400 plant hosts, including numerous economically important crops such as Brassica species. The limited efficacy and environmental concerns associated with chemical control strategies underscore the need for sustainable and targeted alternatives. In [...] Read more.

Xanthomonas species are Gram-negative bacterial pathogens responsible for diseases in over 400 plant hosts, including numerous economically important crops such as Brassica species. The limited efficacy and environmental concerns associated with chemical control strategies underscore the need for sustainable and targeted alternatives. In this study, we evaluated the suitability and biocontrol efficacy of phages Phi1 and Phi3 to combat Xanthomonas campestris pv. campestris (Xcc) in broccoli plants. Kill-curve assays demonstrated that both phages effectively suppressed Xcc growth across a range of multiplicities of infection. Transmission electron microscopy further confirmed their lytic activity, revealing pronounced structural damage to Xcc cells following phage treatment, accompanied by the subsequent release of phage progeny. To assess host specificity and biosafety, the phages were tested against 41 bacterial isolates that were isolated and taxonomically characterized from broccoli and cauliflower in this study. Neither Phi1 nor Phi3 exhibited lytic activity against any non-target isolate, indicating high host specificity and minimal risk to the native Brassica-associated microbiota. In planta assays demonstrated that the combined application of Phi1 and Phi3 reduced Xcc-induced symptom severity in broccoli plants by 80%. Collectively, these results demonstrate that phages Phi1 and Phi3 represent effective and biologically precise agents for the control of black rot disease in Brassica crops. Full article

(This article belongs to the Special Issue Phage Cocktails: Promising Approaches Against Infections)

12 pages, 1540 KB

Open AccessArticle

Screening Ticks for Crimean–Congo Hemorrhagic Fever Virus and Aigai Virus in Greece

by Katerina Tsioka, Smaragda Sotiraki, Danai Pervanidou, Styliani Pappa, Konstantina Stoikou, Annita Vakali, Chrisovaladou-Niki Kefaloudi, Christina Sapanidou, Panagiota Ligda, Angeliki Liakata, Anastasios Saratsis, Dimitrios Chatzidimitriou and Anna Papa

Viruses 2026, 18(5), 483; https://doi.org/10.3390/v18050483 - 22 Apr 2026

Abstract

Ixodid ticks are vectors for a plethora of pathogens, including the Crimean–Congo hemorrhagic fever virus (CCHFV), which causes severe disease in humans. Two autochthonous CCHF human cases were reported in 2025 in Greece. The aim of the present study was to gain a [...] Read more.

Ixodid ticks are vectors for a plethora of pathogens, including the Crimean–Congo hemorrhagic fever virus (CCHFV), which causes severe disease in humans. Two autochthonous CCHF human cases were reported in 2025 in Greece. The aim of the present study was to gain a better insight into the geographic distribution and prevalence of CCHFV and the related Aigai virus (AIGV) in ticks in Greece. Therefore, 680 ticks (135 Hyalomma and 545 Rhipicephalus ticks) collected during 2024 from livestock (sheep, goats, cattle) and from the environment were tested for CCHFV and AIGV. AIGV was detected in 12 adult Rhipicephalus bursa ticks (12/511, 2.3%), while all Hyalomma ticks and R. bursa nymphs were negative for both viruses. AIGV-positive ticks were collected in May and June from goats and sheep in two distantly located regional units of Greece. AIGV sequences from partial S RNA segment differ from the prototype AIGV strain (AP-92) by 10.3% and 1.4% at the nucleotide and amino acid level, respectively. Integrated surveillance studies are needed in ticks, humans, wild and domestic animals within a One Health framework to gain a better insight into the epidemiology of CCHF in Greece, while clinical research is needed to elucidate the impact of AIGV in public health. Full article

(This article belongs to the Special Issue Tick-Borne Viruses: Transmission and Surveillance, 2nd Edition)

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18 pages, 1244 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

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)

17 pages, 926 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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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, 5615 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

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)

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

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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