Viruses

2 pages, 159 KB

Open AccessComment

Comment on Rinaldi et al. Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study. Viruses 2025, 17, 251

by Muhammad Hassan Saeed, Muhammad Ahmed Zaheer, Bhunesh Kumar, Arslan Ali and Muhammad Ahmed Shaikh

Viruses 2025, 17(9), 1227; https://doi.org/10.3390/v17091227 (registering DOI) - 8 Sep 2025

Abstract

Hepatitis D virus (HDV) infection poses a serious global health burden due to its rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma [...] Full article

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

13 pages, 725 KB

Open AccessReview

Fc-Mediated Effector Functions of Anti-NS1 Antibodies in Dengue

by Romchat Kraivong

Viruses 2025, 17(9), 1226; https://doi.org/10.3390/v17091226 (registering DOI) - 7 Sep 2025

Abstract

The non-structural protein 1 (NS1) of dengue virus (DENV) plays a multifaceted role in viral pathogenesis and immune modulation. Although vaccine strategies have traditionally focused on neutralizing antibodies against the envelope (E) protein, recent evidence highlights the protective potential of anti-NS1 antibodies—particularly those [...] Read more.

The non-structural protein 1 (NS1) of dengue virus (DENV) plays a multifaceted role in viral pathogenesis and immune modulation. Although vaccine strategies have traditionally focused on neutralizing antibodies against the envelope (E) protein, recent evidence highlights the protective potential of anti-NS1 antibodies—particularly those that mediate Fc-dependent effector functions. These functions include antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), which collectively bridge adaptive antibody responses with innate immune activation. However, the outcomes of anti-NS1 responses are context-dependent: certain antibody specificities confer protection, while others may contribute to immunopathology. In this review, I synthesize current evidence on the roles of anti-NS1 antibodies in modulating Fc receptor engagement, subclass-specific responses, glycosylation patterns, and their effector functions. Understanding these mechanisms is essential for guiding rational vaccine design and the development of antibody-based diagnostics and therapeutics. By integrating the findings from both innate and adaptive immunology, this review emphasizes the importance of NS1 as a multifunctional immune determinant in dengue virus infection. Full article

(This article belongs to the Special Issue Innate and Adaptive Immune Responses to Arbovirus Infections)

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22 pages, 1773 KB

Open AccessArticle

Comprehensive Analysis of the Impact of Weight Loss Thresholds on Mouse Models of Fatal Viral Infection

by Devin Kenney, Mao Matsuo, Giulia Unali, Alan Wacquiez, Mohsan Saeed and Florian Douam

Viruses 2025, 17(9), 1225; https://doi.org/10.3390/v17091225 (registering DOI) - 7 Sep 2025

Abstract

Preclinical studies in virological research are pivotal to comprehend mechanisms of viral virulence and pathogenesis and evaluate antiviral therapies or vaccines. Mouse models, through access to various genetic strains and amenable reagents, along with their ease of implementation and cost-effectiveness, remain the gold [...] Read more.

Preclinical studies in virological research are pivotal to comprehend mechanisms of viral virulence and pathogenesis and evaluate antiviral therapies or vaccines. Mouse models, through access to various genetic strains and amenable reagents, along with their ease of implementation and cost-effectiveness, remain the gold standard for establishing go/no-go thresholds before advancing to non-human primate or clinical studies. In preclinical mouse studies, standardized weight loss thresholds (WLTs)—which correspond to an established percentage of weight change at which animals are humanely euthanized—are a routine metric to quantitatively evaluate the lethality of a viral pathogen and the effectiveness of antiviral countermeasures in preventing fatal viral disease. While it is recognized that WLTs can significantly impact the assessment of viral virulence, they are often established to meet existing ethical or methodological requirements, rather than being based on a specific scientific rationale. Here, we examine how various experimental variables—including mouse and viral strains and the sex ratio within a mouse cohort—influence the ability of a WLT to support the generation of robust mouse models of fatal viral infection. Using various mouse strains and viral pathogens, we report that variations in experimental conditions in mouse preclinical studies can significantly compromise the performance of a non-adjusted WLT to yield an accurate estimate of viral virulence. Our findings advocate for a robust adjustment of WLT to each experimental framework and associated variables to establish mouse models of fatal viral infection that can generate high-resolution data acquisition while upholding ethical standards. Overall, our study provides methodological insights to enhance the unbiased acquisition and benchmarking of viral virulence and antiviral efficacy data in mouse models. Full article

(This article belongs to the Section General Virology)

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26 pages, 3043 KB

Open AccessArticle

Monocyte Dynamics in Chikungunya Fever: Sustained Activation and Vascular-Coagulation Pathway Involvement

by Caroline Fernandes dos Santos, Priscila Conrado Guerra Nunes, Victor Edgar Fiestas-Solorzano, Mariana Gandini, Flavia Barreto dos Santos, Roberta Olmo Pinheiro, Luís Jose de Souza, Paulo Vieira Damasco, Luzia Maria de Oliveira Pinto and Elzinandes Leal de Azeredo

Viruses 2025, 17(9), 1224; https://doi.org/10.3390/v17091224 (registering DOI) - 7 Sep 2025

Abstract

Chikungunya fever (CF), caused by the Chikungunya virus (CHIKV), is characterized by disabling symptoms such as joint pain that can last for months. Monocytes play a central role in immune modulation and viral replication during infection. This study evaluated the clinical and immunological [...] Read more.

Chikungunya fever (CF), caused by the Chikungunya virus (CHIKV), is characterized by disabling symptoms such as joint pain that can last for months. Monocytes play a central role in immune modulation and viral replication during infection. This study evaluated the clinical and immunological profiles of patients with laboratory-confirmed CF. Fever and joint pain were the most frequently reported symptoms, whereas edema was more common in women. CHIKV-infect individuals exhibited increased TLR4 expression in non-classical monocytes (CD14+CD16++). Additionally, intermediate (CD14+CD16+) and non-classical (CD14+CD16++) monocytes expressing TLR7 were enriched during the acute phase and in some chronic patients, thereby suggest prolonged TLR7 pathway activation. Levels of soluble CD163 (sCD163)—a marker of monocyte/macrophage activation—were elevated as well, indicating sustained immune activation. Coagulation-related mediators—including Tissue factor (TF) and Tissue factor pathway inhibitor (TFPI)—also increased, despite the rarity of hemorrhagic events or thrombocytopenia. Patients with arthritis demonstrated higher frequencies of TLR7+ intermediate monocytes and elevated Epidermal growth factor (EGF) levels, whereas those with edema exhibit increased Vascular endothelial growth factor (VEGF) levels. Overall, these findings highlighted the differential activation of CD16+ monocytes and suggested that sCD163 is a marker of monocyte/macrophage activation during CHIKV infection. Full article

(This article belongs to the Special Issue Recent Advances on Arboviruses Pathogenesis and Evolution)

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11 pages, 654 KB

Open AccessArticle

The Role of HBx Mutations in Chronic Hepatitis B with Acute Exacerbation

by Xiaobei Chen, Jinzhi Shi, Ping Zhou, Yunyun Tian, Yajing Zheng, Tingting Liu, Yan Li and Fan Zhu

Viruses 2025, 17(9), 1223; https://doi.org/10.3390/v17091223 (registering DOI) - 7 Sep 2025

Abstract

Hepatitis B virus (HBV) infection remains a significant global health burden, primarily due to its chronic complications, including acute exacerbation, cirrhosis, hepatocellular carcinoma (HCC), and related sequelae. Acute exacerbation of chronic hepatitis B (CHB-AE) is common and often represents the earliest clinical manifestation. [...] Read more.

Hepatitis B virus (HBV) infection remains a significant global health burden, primarily due to its chronic complications, including acute exacerbation, cirrhosis, hepatocellular carcinoma (HCC), and related sequelae. Acute exacerbation of chronic hepatitis B (CHB-AE) is common and often represents the earliest clinical manifestation. The Hepatitis B virus X protein (HBx) (17-kDa) is not only essential for viral replication but also plays a role in the development of HCC. To investigate the role of HBx mutation in CHB-AE progression, we enrolled 33 hospitalized CHB-AE patients and 31 patients with HBV-related liver failure (controls) from mainland China between January 2017 and June 2018. Single mutation 36 of HBx was significantly more prevalent in CHB-AE patients (p < 0.05), whereas Joint Mutation 1 was more frequent in HBV-related liver failure patients (p < 0.05). HBx mutations, including Single mutation 36 and Joint Mutations 2 and 3, were significantly associated with high HBV DNA levels (p < 0.05), while Joint mutation 1 predominated in the low HBV DNA group (p < 0.01). Age-stratified analysis showed that Single mutation 36 and Joint Mutation 2 were more common in younger patients (<35 years old) (p < 0.05), whereas Joint mutation 1 was more frequent in older age (≥35 years old) (p < 0.05). Moreover, antiviral therapy markedly reduced the prevalence of Joint mutation 1 from 82.98% in treatment-naïve patients to 29.41% in treatment-experienced patients (p < 0.0001). These findings suggest that specific HBx mutations are associated with viral replication levels, disease progression, and patient demographics. Such mutations may serve as molecular markers for disease severity and potential therapeutic targets in both CHB-AE and HBV-related liver failure. Full article

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

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18 pages, 5578 KB

Open AccessArticle

Insights into Novel Viral Threats in Sweetpotato from Burkina Faso: Characterisation of Unexplored Pathogens

by Pakyendou E. Name, Ezechiel B. Tibiri, Fidèle Tiendrébéogo, Seydou Sawadogo, Florencia Djigma, Lassina Traoré, Angela O. Eni and Justin S. Pita

Viruses 2025, 17(9), 1222; https://doi.org/10.3390/v17091222 (registering DOI) - 7 Sep 2025

Abstract

Sweetpotato is a key staple crop in tropical and subtropical regions. Its vegetative propagation makes it a persistent reservoir, facilitating the emergence and spread of complex infections. Understanding its virome is crucial for disease management and food security. We investigated the sweetpotato virome [...] Read more.

Sweetpotato is a key staple crop in tropical and subtropical regions. Its vegetative propagation makes it a persistent reservoir, facilitating the emergence and spread of complex infections. Understanding its virome is crucial for disease management and food security. We investigated the sweetpotato virome in Burkina Faso using rolling circle amplification and Oxford Nanopore sequencing. Eight symptomatic leaf samples, previously undiagnosed using conventional methods, were analysed. Bioinformatic pipelines were employed followed by phylogenetic comparisons. Two viruses known to infect sweetpotato, namely sweet potato leaf curl virus (SPLCV) and sweet potato leaf curl deltasatellite 3 (SPLCD3), were consistently detected in all samples. Additionally, pepper yellow vein Mali virus (PepYVMV), cotton leaf curl Gezira alphasatellite (CLCuGeA) and cotton leaf curl Gezira betasatellite (CLCuGeB) were identified for the first time in this crop. Phylogenetic analysis confirmed their genetic proximity to isolates from tomato, okra and pepper. Their co-occurrence with SPLCV and SPLCD3 indicates a complex viral landscape that could influence disease severity. This study highlights the underestimated role of sweetpotato as a viral reservoir, influencing virus evolution and transmission. Further studies should assess their pathogenicity, co-infection dynamics and vector-mediated transmission to improve crop productivity. Full article

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

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18 pages, 1343 KB

Open AccessReview

A Critical Review of Bovine Viral Diarrhea Virus: Spotlights on Host Plasticity and Potential Spillover Events

by Eaftekhar Ahmed Rana, M. Asaduzzaman Prodhan, Joshua W. Aleri, Syeda Hasina Akter, Henry Annandale, Sam Abraham, Subir Sarker, Jully Gogoi-Tiwari and Jasim Muhammad Uddin

Viruses 2025, 17(9), 1221; https://doi.org/10.3390/v17091221 (registering DOI) - 7 Sep 2025

Abstract

The bovine viral diarrhea virus (BVDV) infects a wide range of domestic and wild mammals. This review hypothesized that there might be cross-species transmission of BVDV. Therefore, the aim was to explore the BVDV-5′ UTR and N-pro sequence-based evidence to understand host plasticity [...] Read more.

The bovine viral diarrhea virus (BVDV) infects a wide range of domestic and wild mammals. This review hypothesized that there might be cross-species transmission of BVDV. Therefore, the aim was to explore the BVDV-5′ UTR and N-pro sequence-based evidence to understand host plasticity among different animals. A total of 146 unique BVDV sequences retrieved from GenBank, originating from 12 distinct mammalian species that are submitted from 55 countries, were analyzed. The phylogenetic analysis revealed that all three BVDV species exhibited genetic relatedness infecting diverse animal species. BVDV-1 sequences obtained from cattle, buffalo, and pigs and BVDV-2 and HoBi-like pestivirus sequences from cattle, goats, and sheep showed a genetic resemblance. Surprisingly, cattle and buffalo in China, cattle and yak in Mongolia, cattle and wild boar in Serbia, cattle and deer in Mexico, cattle and alpacas in Canada, goats and pigs in the USA, and sheep and buffalo in Argentina were infected with BVDV-1 within the same county and strongly positioned in the same cluster, indicating potential spillover with host tropism. Moreover, BVDV sequences isolated from various neighboring countries clustered closely, suggesting potential cross-border transmission events. Based on genomic evidence, the BVDV transmission cycle could be depicted, where cattle act as a primary source of infection, while other domestic and wild animals maintain the infection ecology within their habitat due to virus tropism. Full article

(This article belongs to the Section Animal Viruses)

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25 pages, 9428 KB

Open AccessArticle

Generation and Characterization of HDV-Specific Antisera with Respect to Their Application as Specific and Sensitive Research and Diagnostic Tools

by Keerthihan Thiyagarajah, Sascha Hein, Jan Raupach, Nirmal Adeel, Johannes Miller, Maximilian Knapp, Christoph Welsch, Mirco Glitscher, Esra Görgülü, Philipp Stoffers, Pia Lembeck, Jonel Trebicka, Sandra Ciesek, Kai-Henrik Peiffer and Eberhard Hildt

Viruses 2025, 17(9), 1220; https://doi.org/10.3390/v17091220 (registering DOI) - 7 Sep 2025

Abstract

The hepatitis D virus (HDV) is a small, defective RNA virus that induces the most severe form of viral hepatitis. Despite its severity, HDV infections are under-diagnosed due to non-standardized and costly diagnostic screening methods. However, limited research has been conducted on characterizing [...] Read more.

The hepatitis D virus (HDV) is a small, defective RNA virus that induces the most severe form of viral hepatitis. Despite its severity, HDV infections are under-diagnosed due to non-standardized and costly diagnostic screening methods. However, limited research has been conducted on characterizing HDV-specific antibodies as alternative tools for diagnosis. Thus, we generated HDV-specific, polyclonal antibodies by immunizing rabbits with the HDV protein, small hepatitis delta antigen (SHDAg), in its oligomeric or denatured form. We identified SHDAg-specific linear epitopes by peptide array analysis and compared them to epitopes identified in HDV-infected patients. Using in silico structural analysis, we show that certain highly immunogenic domains in SHDAg, such as the coiled-coil domain, are masked in the oligomeric conformation of the protein; others, such as the second arginine-rich motif, are exposed. The nuclear localization signal is presumably exposed only by specific interaction of oligomeric HDAg with the HDV-RNA genome. Through surface plasmon resonance analysis, we identified two polyclonal antibodies derived from rabbit antisera with affinities in the lower nanomolar range. These antibodies were used to establish an ELISA that can quantitatively detect HDV virions in vitro and upon further optimization could be used as a promising alternative diagnostic screening method. Full article

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

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15 pages, 647 KB

Open AccessReview

Hypochlorous Acid (HOCl) as a Promising Respiratory Antiseptic

by Michael Winter, Dirk Boecker and Wilfried Posch

Viruses 2025, 17(9), 1219; https://doi.org/10.3390/v17091219 (registering DOI) - 7 Sep 2025

Abstract

The COVID-19 pandemic has inflicted unprecedented pressure on communities and healthcare systems around the world. An outstandingly broad and intensive investigation of possible therapeutic interventions is currently taking place to prevent similar future threats to the global population. Investigating the related mechanisms of [...] Read more.

The COVID-19 pandemic has inflicted unprecedented pressure on communities and healthcare systems around the world. An outstandingly broad and intensive investigation of possible therapeutic interventions is currently taking place to prevent similar future threats to the global population. Investigating the related mechanisms of action is often complex and time consuming. Moreover, research on biochemical interactions of new drugs involves a considerable amount of effort, consequently bearing inherent financial and operational risks for pharmaceutical companies. An interesting approach to counteract colonization and infection is the concept of antiseptic treatment in vivo. Antiseptics are cost-effective and globally accessible, due to their ease of production, transportation and handling. A broad spectrum of active agents with different properties is readily available. One of these substances is hypochlorous acid (HOCl), which is also a naturally occurring biocidal agent and as such part of the innate immune system. Its successful history of medical use in wound treatment, combined with low cytotoxicity and documented efficacy against various pathogens, suggests that HOCl might be an effective agent for treating the respiratory mucosa. This could potentially enable therapeutic inhalation for combating bacterial infections and viral pathogens such as human respiratory syncytial, influenza, and SARS-CoV-2 viruses, which will be discussed in the present article. Full article

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

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13 pages, 524 KB

Open AccessReview

Codon Usage Bias in Human RNA Viruses and Its Impact on Viral Translation, Fitness, and Evolution

by Iván Ventoso

Viruses 2025, 17(9), 1218; https://doi.org/10.3390/v17091218 (registering DOI) - 6 Sep 2025

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Abstract

Synonymous codon usage (codon bias) greatly influences not only translation but also mRNA stability. In vertebrates, highly expressed genes preferentially use codons with an optimal tRNA adaptation index (tAI) that mostly end in C or G. Surprisingly, the codon usage of viruses infecting [...] Read more.

Synonymous codon usage (codon bias) greatly influences not only translation but also mRNA stability. In vertebrates, highly expressed genes preferentially use codons with an optimal tRNA adaptation index (tAI) that mostly end in C or G. Surprisingly, the codon usage of viruses infecting humans often deviates from optimality, showing an enrichment in A/U-ending codons, which are generally associated with slow decoding and reduced mRNA stability. This observation is particularly evident in RNA viruses causing respiratory illnesses in humans. This review analyzes the mutational and selective forces that shape nucleotide composition and codon usage drift in human RNA viruses, as well as their impact on translation, viral fitness, and evolution. It also describes how some viruses overcome suboptimal codon usage to outcompete host mRNA for translation. Finally, the roles of viral tropism and host adaptation in codon usage bias of prototypical viruses are discussed. Full article

(This article belongs to the Special Issue Viral Strategies and Cellular Countermeasures That Regulate mRNA Access to the Translation Apparatus: 2nd Edition)

10 pages, 914 KB

Open AccessArticle

Absence of West Nile and Usutu Virus Persistence in Overwintering Mosquitoes in Northeastern France: Insights from Cold-Season Surveillance

by Pauline Jourdan, Jean-Philippe Martinet, Hubert Ferté, Bruno Mathieu, Marie Vazeille, Jérôme Depaquit, Anna-Bella Failloux, Anouk Decors and Rémi Charrel

Viruses 2025, 17(9), 1217; https://doi.org/10.3390/v17091217 (registering DOI) - 6 Sep 2025

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Abstract

Emerging arboviruses of the Orthoflavivirus genus such as West Nile virus (WNV) and Usutu virus (USUV), primarily transmitted by Culex mosquitoes, pose significant public health threats due to their ability to cause severe neurological diseases in humans and animals. While studies in North [...] Read more.

Emerging arboviruses of the Orthoflavivirus genus such as West Nile virus (WNV) and Usutu virus (USUV), primarily transmitted by Culex mosquitoes, pose significant public health threats due to their ability to cause severe neurological diseases in humans and animals. While studies in North America and Central Europe have shown that these viruses can persist in overwintering mosquitoes, their role in viral maintenance during the cold season in northeastern France remains unknown. This study aimed to assess whether overwintering female mosquitoes in this region could harbor WNV or USUV during the cold season, potentially maintaining viral circulation until the following transmission season. Between October 2021 and February 2024, a total of 10,617 overwintering female mosquitoes were collected in various types of habitats across five departments in northeastern France. The most common species was Culex pipiens (88%). Mosquitoes were grouped into 1121 pools (1–10 individuals each) and tested by real-time RT-PCR for WNV, USUV, and other flaviviruses using a pan-Flavivirus NS5-targeting assay. All pools tested negative, indicating no evidence of viral RNA in overwintering females. These results suggested that overwintering female mosquitoes in northeastern France do not act as reservoirs for WNV or USUV, and do not contribute to their overwintering maintenance. Full article

(This article belongs to the Section Invertebrate Viruses)

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10 pages, 447 KB

Open AccessArticle

Tixagevimab-Cilgavimab Effectively Prevents COVID-19 Infection in Patients with End-Stage Kidney Disease

by Noppakao Kongtal, Watchara Pichitsiri, Supinda Sirilak, Anyarin Wannakittirat, Busakorn Sontham, Sagoontee Inkate and Theerachai Thammathiwat

Viruses 2025, 17(9), 1216; https://doi.org/10.3390/v17091216 (registering DOI) - 6 Sep 2025

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Abstract

Patients with end-stage kidney disease (ESKD) often exhibit suboptimal responses to COVID-19 vaccination. Tixagevimab-Cilgavimab, a neutralizing long-acting antibody (LAAB), has demonstrated effectiveness in preventing severe COVID-19 and hospitalization among immunocompromised populations. This study aimed to evaluate the efficacy and safety of Tixagevimab-Cilgavimab in [...] Read more.

Patients with end-stage kidney disease (ESKD) often exhibit suboptimal responses to COVID-19 vaccination. Tixagevimab-Cilgavimab, a neutralizing long-acting antibody (LAAB), has demonstrated effectiveness in preventing severe COVID-19 and hospitalization among immunocompromised populations. This study aimed to evaluate the efficacy and safety of Tixagevimab-Cilgavimab in ESKD patients receiving hemodialysis, peritoneal dialysis, or kidney transplantation. This single-center, retrospective cohort study was conducted at Naresuan University Hospital, Phitsanulok, Thailand, and included patients with end-stage kidney disease (ESKD) receiving maintenance hemodialysis, peritoneal dialysis, or kidney transplantation between June 2022 and June 2023, during the peak of the Omicron variant. Patients who received a single 150/150 mg dose of Tixagevimab-Cilgavimab were compared to those who did not, in terms of time to first COVID-19 infection and hospitalization within 6 months. Cox proportional hazards models were used to evaluate associations, adjusted for age, sex, type 2 diabetes, dyslipidemia, systolic and diastolic blood pressure, serum creatinine, number of COVID-19 vaccine doses, and prior COVID-19 infection. Safety was assessed by comparing creatine kinase (CK) levels before and after treatment using generalized estimating equations (GEE). Of 117 patients, 58 received Tixagevimab-Cilgavimab (mean age 59 ± 15 years); 92% were on dialysis and 8% had undergone kidney transplantation. COVID-19 infection occurred in 10.3% of the LAAB group versus 11.9% in the control group. In the adjusted Cox model, LAAB use was significantly associated with a reduced risk of COVID-19 infection (adjusted HR: 0.20; 95% CI: 0.04–0.95; p = 0.043). No variables were significantly associated with hospitalization, although LAAB use showed a non-significant trend toward reduced hospitalization risk (adjusted HR: 0.08; 95% CI: 0.01–1.56; p = 0.096). No local or systemic adverse effects were reported. CK levels remained unchanged after administration. Tixagevimab-Cilgavimab was effective in reducing the risk of COVID-19 infection among ESKD patients, without evidence of adverse effects, supporting its use as a prophylactic agent in this high-risk population. Full article

(This article belongs to the Special Issue Humoral Immune Response to Viruses)

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20 pages, 3026 KB

Open AccessArticle

Biomarker-Based Risk Assessment Strategy for Long COVID: Leveraging Spike Protein and Proinflammatory Mediators to Inform Broader Postinfection Sequelae

by Ying-Fei Yang, Min-Pei Ling, Szu-Chieh Chen, Yi-Jun Lin, Shu-Han You, Tien-Hsuan Lu, Chi-Yun Chen, Wei-Min Wang, Si-Yu Chen, I-Hsuan Lai, Huai-An Hsiao and Chung-Min Liao

Viruses 2025, 17(9), 1215; https://doi.org/10.3390/v17091215 - 5 Sep 2025

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Abstract

Long COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, has emerged as a significant public health challenge with wide-ranging clinical and socioeconomic implications. Developing an effective risk assessment strategy is essential for the early identification and management of individuals susceptible to prolonged [...] Read more.

Long COVID, characterized by persistent symptoms following acute SARS-CoV-2 infection, has emerged as a significant public health challenge with wide-ranging clinical and socioeconomic implications. Developing an effective risk assessment strategy is essential for the early identification and management of individuals susceptible to prolonged symptoms. This study uses a quantitative approach to characterize the dose–response relationships between spike protein concentrations and effects, including Long COVID symptom numbers and the release of proinflammatory mediators. A mathematical model is also developed to describe the time-dependent change in spike protein concentrations post diagnosis in twelve Long COVID patients with a cluster analysis. Based on the spike protein concentration–Long COVID symptom numbers relationship, we estimated a maximum symptom number (~20) that can be used to reflect a persistent predictor. We found that among the crucial biomarkers associated with Long COVID proinflammatory mediator, CXCL8 has the lowest 50% effective dose (0.01 μg mL⁻¹), followed by IL-6 (0.39), IL-1β (0.46), and TNF-α (0.56). This work provides a comprehensive risk assessment strategy with dose–response tools and mathematical modeling developed to estimate potential spike protein concentration. Our study suggests persistent Long COVID guidelines for personalized care strategies and could inform public health policies to support early interventions that reduce long-term disability and healthcare burdens with possible other post-infection syndromes. Full article

(This article belongs to the Section Coronaviruses)

15 pages, 3004 KB

Open AccessArticle

Phylogenetic and Molecular Evolutionary Insights into Monkeypox Virus Circulation in Shenzhen, China, 2023–2024

by Chuan Shi, Xiaochen Zheng, Lei Lei, Jinhui Xiao, Guangqing Yu, Yingdong Li, Zhifeng Ma, Minjie Li, Yanling Zeng, Ziquan Lv, Yixiong Chen, Wei Tan and Qianru Wang

Viruses 2025, 17(9), 1214; https://doi.org/10.3390/v17091214 - 5 Sep 2025

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Abstract

The 2022 global mpox outbreak highlighted the risk of sustained human-to-human transmission of monkeypox virus (MPXV) in non-endemic regions, yet genomic surveillance in Asia, particularly in China, remains limited. This study conducted horizontal genomic surveillance of MPXV in Shenzhen from 2023 to 2024 [...] Read more.

The 2022 global mpox outbreak highlighted the risk of sustained human-to-human transmission of monkeypox virus (MPXV) in non-endemic regions, yet genomic surveillance in Asia, particularly in China, remains limited. This study conducted horizontal genomic surveillance of MPXV in Shenzhen from 2023 to 2024 to characterize the phylogenetic structure, mutational patterns, and adaptive evolution of locally circulating strains. Phylogenetic analysis showed 95.2% of strains belonged to the dominant lineage C.1.1, with 4.8% in lineage E.3, forming three distinct genetic clusters that indicate multiple independent introductions and established local transmission chains. Whole-genome mutational analysis identified 146 single-nucleotide polymorphisms (SNPs), 81.5% of which carried APOBEC3-mediated mutation signatures (TC > TT and GA > AA), reflecting host-driven antiviral editing. Notably, dynamic changes in low-complexity regions (LCRs) were observed, implying potential roles in genome plasticity and adaptive evolution. Functional analysis revealed non-synonymous substitution biases in host-interacting proteins OPG064, OPG145, and OPG210, while replication protein OPG105 remained conserved. Structural modeling identified critical substitutions in OPG002 (S54F), OPG016 (R84K), and OPG036 (R48C) that may enhance immune evasion by modulating TNF-α signaling, NKG2D engagement, and Type I interferon antagonism. These findings illuminate unique MPXV evolutionary dynamics in Shenzhen, emphasizing continuous genomic surveillance for non-endemic outbreak preparedness. Full article

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

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12 pages, 4871 KB

Open AccessFeature PaperArticle

Construction and Segmental Reconstitution of Full-Length Infectious Clones of Milk Vetch Dwarf Virus

by Aamir Lal, Muhammad Amir Qureshi, Man-Cheol Son, Sukchan Lee and Eui-Joon Kil

Viruses 2025, 17(9), 1213; https://doi.org/10.3390/v17091213 - 5 Sep 2025

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Abstract

The construction of infectious clones (ICs) is essential for studying viral replication, pathogenesis, and host interactions. Milk vetch dwarf virus (MDV), a nanovirus with a multipartite, single-stranded DNA genome, presents unique challenges for IC development due to its segmented genome organization. To enable [...] Read more.

The construction of infectious clones (ICs) is essential for studying viral replication, pathogenesis, and host interactions. Milk vetch dwarf virus (MDV), a nanovirus with a multipartite, single-stranded DNA genome, presents unique challenges for IC development due to its segmented genome organization. To enable functional analysis of its genome, we constructed full-length tandem-dimer-based ICs for all eight MDV genomic segments. Each segment was cloned into a binary vector and co-delivered into Nicotiana benthamiana, Nicotiana tabacum, Vicia faba, and Vigna unguiculata plants via Agrobacterium-mediated inoculation. Systemic infection was successfully reconstituted in all host plants, with PCR-based detection confirming the presence of all viral segments in the infected leaves of nearly all tested plants. Segmental accumulation in infected plants was quantified using qPCR, revealing non-equimolar distribution across hosts. This study establishes the first complete IC system for MDV, enabling reproducible infection, replication analysis, and quantitative segment profiling. It provides a foundational tool for future molecular investigations into MDV replication, host interactions, and viral movement, advancing our understanding of nanovirus biology and transmission dynamics. Full article

(This article belongs to the Special Issue Application of Genetically Engineered Plant Viruses)

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14 pages, 1048 KB

Open AccessArticle

Antiretroviral Adherence and Use of Antihypertensives, Statins, and Antidiabetics Among Elderly People with HIV: A 5-Year Real-World Study in Southern Italy

by Pietro Trisolini, Simona Cammarota, Anna Citarella, Marianna Fogliasecca, Viviana Alicchio, Stefania Antonacci, Romina Giannini, Renato Lombardi, Mariantonietta Piccoli, Francesco Pomarico, Cataldo Procacci, Antonino Siniscalco, Stefania Spennato, Annalisa Saracino and Sergio Lo Caputo

Viruses 2025, 17(9), 1212; https://doi.org/10.3390/v17091212 - 5 Sep 2025

Viewed by 249

Abstract

Modern antiretroviral therapy (ART) has transformed HIV into a chronic, manageable condition. This retrospective analysis of administrative data from Apulia (Southern Italy) covering 2018–2023 evaluated demographic changes, ART regimen trends, adherence, and the use of antihypertensives, statins, and antidiabetics among people with HIV [...] Read more.

Modern antiretroviral therapy (ART) has transformed HIV into a chronic, manageable condition. This retrospective analysis of administrative data from Apulia (Southern Italy) covering 2018–2023 evaluated demographic changes, ART regimen trends, adherence, and the use of antihypertensives, statins, and antidiabetics among people with HIV (PWH). Temporal trends were assessed using compound annual growth rate (CAGR). ART adherence was measured as proportion of days covered (PDC), categorized as <75%, 75–90%, and ≥90%. Over the study period, the proportion of PWH aged 18–54 declined, while those aged 55–64 and ≥65 increased (CAGRs: +10.9%, +14.3%). Use of single-tablet regimens rose from 45.1% to 79.6% (CAGR +12.1%), and integrase-based regimens increased from 52.0% to 69.0%, while protease inhibitor and multi-tablet regimens declined. Antihypertensives were the most prescribed concomitant drugs, followed by statins and antidiabetics (CAGRs: +5.8%, +9.7%, +9.5%). In 2023, 81.9% of subjects achieved PDC ≥ 90%, although lower adherence was observed in women and treatment-naïve individuals. These findings indicate a shift toward simplified, integrase-based regimens and high ART adherence, alongside a growing cardiometabolic burden. Tailored strategies are needed to support adherence, particularly in women and treatment-naïve individuals, and to address cardiovascular risk in aging PWH. Full article

(This article belongs to the Special Issue HIV in the Context of Chronic Disorders and Aging)

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16 pages, 2280 KB

Open AccessArticle

Modification of H1N1 Influenza Luciferase Reporter Viruses Using StopGo Translation and/or Mouse-Adapted Mutations

by Po-Ling Chen, Guohua Yang, Chet Ojha, Balaji Banoth and Charles J. Russell

Viruses 2025, 17(9), 1211; https://doi.org/10.3390/v17091211 - 5 Sep 2025

Viewed by 297

Abstract

Reporter viruses are valuable tools for studying infections at the cellular level and in living animals. They also enable rapid, high-throughput antiviral drug screening and serological studies. We previously developed a bioluminescence-based reporter virus, rTN09-PA-Nluc, derived from influenza A/Tennessee/1-560/2009 (TN09, pH1N1) in which [...] Read more.

Reporter viruses are valuable tools for studying infections at the cellular level and in living animals. They also enable rapid, high-throughput antiviral drug screening and serological studies. We previously developed a bioluminescence-based reporter virus, rTN09-PA-Nluc, derived from influenza A/Tennessee/1-560/2009 (TN09, pH1N1) in which a NanoLuc (Nluc) reporter protein was fused to the PA protein. Reduced growth of rTN09-PA-Nluc in MDCK cells and mice was restored by mutations arising from mouse adaptation. Here, to test the hypothesis that the growth defect resulted from the PA-Nluc protein fusion, we generated the luciferase reporter virus rTN09-PA-Nluc/SG, which undergoes StopGo translation to yield separate PA and NLuc proteins along with a proportion of the PA-Nluc fusion. The rTN09-PA-Nluc/SG virus had greater protein expression and increased replication in MDCK cells compared to rTN09-PA-Nluc. The reporter virus encoding StopGo translation was superior to the virus without it in bioluminescence-based virus neutralization assays in vitro, providing results in 24 h as opposed to 3 days using unmodified influenza virus and standard neutralization assay protocols. However, the reporter virus encoding StopGo translation remained attenuated in mice. Mouse-adaptive mutations were needed for full virulence and efficient non-invasive imaging in mice. Overall, these findings demonstrate the benefit of incorporating StopGo translation into influenza reporter viruses for in vitro assays, yet mouse-adapted mutations appeared superior in mice. Full article

(This article belongs to the Section Animal Viruses)

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13 pages, 26521 KB

Open AccessArticle

Development of a Safe and Effective mRNA Candidate Vaccine Against PEDV G2c Genotype Infection

by Shixuan Zhu, Nan Cao, Huawei Zhang and Leqiang Sun

Viruses 2025, 17(9), 1210; https://doi.org/10.3390/v17091210 - 4 Sep 2025

Viewed by 261

Abstract

Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea, dehydration, and high mortality in piglets, leading to significant economic losses in the swine industry. The spike (S) protein of PEDV is the primary target for neutralizing antibodies and [...] Read more.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea, dehydration, and high mortality in piglets, leading to significant economic losses in the swine industry. The spike (S) protein of PEDV is the primary target for neutralizing antibodies and is critical for vaccine development. In this study, the pUC57-S01 and pUC57-S02 plasmids carrying the codon-optimized truncated S gene sequence were constructed. The mRNA S01 showed higher protein expression in vitro than mRNA S02, as confirmed by Western blotting. The safety and immunogenicity of mRNA S01 were evaluated in animal experiments. The results indicated that the mRNA S01 vaccine was safe for piglets and pregnant sows. Immunogenicity was assessed by a neutralization assay, which revealed that encapsulated mRNA S01 induced high levels of neutralizing antibody titers in pigs. Challenge protection efficiency tests showed that the mRNA S01 vaccine conferred immunity to newborn piglets, protecting them from a homologous PEDV strain challenge. This study provides a foundation for the clinical application of PEDV mRNA vaccines and offers a reference for the development of novel vaccines against PEDV. Full article

(This article belongs to the Special Issue Porcine Epidemic Diarrhea Virus (PEDV): A Persistent Threat to the Global Swine Industry)

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28 pages, 8441 KB

Open AccessReview

Recombinant Chimeric Virus-like Particles of Human Papillomavirus Produced by Distinct Cell Lineages: Potential as Prophylactic Nanovaccine and Therapeutic Drug Nanocarriers

by Cyntia Silva Oliveira, Dirce Sakauchi, Érica Akemi Kavati Sasaki and Aurora Marques Cianciarullo

Viruses 2025, 17(9), 1209; https://doi.org/10.3390/v17091209 - 4 Sep 2025

Viewed by 453

Abstract

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating [...] Read more.

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

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

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17 pages, 2626 KB

Open AccessArticle

Multivariate Assessment of Thyroid, Lipid, and Inflammatory Profiles by HBV Status and Viral Load: Age- and Sex-Specific Findings

by Hyeokjun Yun, Jong Wan Kim and Jae Kyung Kim

Viruses 2025, 17(9), 1208; https://doi.org/10.3390/v17091208 - 3 Sep 2025

Viewed by 432

Abstract

Chronic hepatitis B virus (HBV) infection may influence extrahepatic systems, including endocrine and lipid regulation. In this cross-sectional study, 186 adults were stratified by HBV DNA status and viral load to examine thyroid function, systemic inflammation, and lipid metabolism, with further analyses by [...] Read more.

Chronic hepatitis B virus (HBV) infection may influence extrahepatic systems, including endocrine and lipid regulation. In this cross-sectional study, 186 adults were stratified by HBV DNA status and viral load to examine thyroid function, systemic inflammation, and lipid metabolism, with further analyses by age and sex. Thyroid-stimulating hormone (TSH, a pituitary regulator of thyroid function) levels were significantly lower in HBsAg-positive individuals compared with controls; however, this association was attenuated after stratification by viral load, indicating that the relationship is not unequivocally independent of HBV DNA levels, as free thyroxine (FT4, the circulating thyroid hormone reflecting gland activity) levels remained stable. Lipid profiles displayed demographic-specific patterns: males with high viral load exhibited lower HDL cholesterol, whereas younger HBV-positive individuals showed higher LDL cholesterol. CRP levels were unaffected by HBV status or viral load, aligning with the absence of systemic inflammation in early or inactive disease stages. Age was a major determinant across biomarkers, with complex interactions involving sex and viral load. These findings indicate subtle but clinically relevant extrahepatic effects of HBV infection and underscore the need for personalized monitoring and longitudinal studies to clarify metabolic and cardiovascular implications. These subgroup trends should be interpreted with caution given the absence of BMI, liver enzyme, fibrosis, medication, and comorbidity data in this retrospective cohort. Full article

(This article belongs to the Special Issue Viral Hepatitis and Liver Diseases)

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30 pages, 2065 KB

Open AccessReview

Mechanisms of Thromboinflammation in Viral Infections—A Narrative Review

by Viviane Lima Batista, Jenniffer Ramos Martins, Celso Martins Queiroz-Junior, Eugenio Damaceno Hottz, Mauro Martins Teixeira and Vivian Vasconcelos Costa

Viruses 2025, 17(9), 1207; https://doi.org/10.3390/v17091207 - 3 Sep 2025

Viewed by 514

Abstract

The circulatory and immune systems function in close coordination to maintain homeostasis and act as a frontline defense against infections. However, under certain conditions, this interaction becomes dysregulated, leading to thromboinflammation, a pathological process marked by the concurrent and excessive activation of coagulation, [...] Read more.

The circulatory and immune systems function in close coordination to maintain homeostasis and act as a frontline defense against infections. However, under certain conditions, this interaction becomes dysregulated, leading to thromboinflammation, a pathological process marked by the concurrent and excessive activation of coagulation, inflammation, and endothelial dysfunction. During viral infections, this phenomenon can markedly worsen clinical outcomes. Evidence indicates that viruses such as dengue, chikungunya, influenza, and SARS-CoV can trigger thromboinflammatory responses involving platelet activation, the release of procoagulant and pro-inflammatory mediators, and the formation of thrombi within blood vessels. While this response may initially help contain viral dissemination, in cases of high viremia it can progress to disseminated intravascular coagulation (DIC), hemorrhage, and multiple organ failure. This review compiles current evidence on thromboinflammatory mechanisms induced by arboviral and respiratory viruses and examines how these processes contribute to diseases’ pathogenesis and clinical severity. Full article

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

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13 pages, 1960 KB

Open AccessArticle

Depletion of Caspase-12 Alleviates Retinal Degeneration in Aged BALB/c Mice Following Systemic Neonatal Infection by Murine Cytomegalovirus (MCMV)

by Jinxian Xu, Xinyan Zhang, Yi Liao, Ting Shi, Brendan Marshall and Ming Zhang

Viruses 2025, 17(9), 1206; https://doi.org/10.3390/v17091206 - 3 Sep 2025

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Abstract

(1) Background: Retinal degeneration develops upon caspase-12 activation in aged BALB/c mice following systemic neonatal infection. (2) Methods: MCMV or medium was injected intraperitoneally (i.p.) into caspase-12^−/− and caspase-12^+/+ mice (on BALB/c background) at <3 days after birth. At 8 and [...] Read more.

(1) Background: Retinal degeneration develops upon caspase-12 activation in aged BALB/c mice following systemic neonatal infection. (2) Methods: MCMV or medium was injected intraperitoneally (i.p.) into caspase-12^−/− and caspase-12^+/+ mice (on BALB/c background) at <3 days after birth. At 8 and 12 months post infection (p.i.), eyes were analyzed by SD-OCT before eyes and extraocular tissues were collected and analyzed by plaque assay, H&E staining, TUNEL assay, Western blot and real-time RT-PCR. (3) Results: Virus DNA, but not replicating virus, was present in eyes and extraocular tissues at 8 and 12 months p.i. Several MCMV genes were expressed in eyes of both MCMV-infected caspase-12^−/− and caspase-12^+/+ mice, while mean retinal thickness was significantly higher in MCMV latently infected aged caspase-12^−/− mice compared to age-matched infected caspase-12^+/+ mice. Although similar levels of cleaved caspase-1 were detected in eyes of both infected caspase-12^−/− and control mice, significantly higher levels of activated NF-κB, cleaved caspase-8, MLKL, p-RIP3 and p53 were observed in eyes of infected caspase-12^+/+ mice compared to eyes of infected caspase-12^−/− mice. (4) Conclusions: Our results suggest that caspase-12 contributes to retinal degeneration during MCMV ocular latency via multiple pathways including apoptosis and necroptosis. Full article

(This article belongs to the Special Issue Unraveling the Pathogenesis of Persistent Virus Infection)

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19 pages, 9929 KB

Open AccessArticle

Development of an Acid-Protective Polymer Encapsulation Formulation for Oral Delivery of Salmonella Phages

by Manju Bernela, Nitin Virmani, Bidhan Chand Bera, Rajesh Kumar Vaid, Medhavi Vashisth and Taruna Anand

Viruses 2025, 17(9), 1205; https://doi.org/10.3390/v17091205 - 2 Sep 2025

Viewed by 367

Abstract

Bacteriophage therapy can successfully provide additional treatment to control Salmonella infection, but low gastric pH limits its oral application. The present study aimed to develop an improved encapsulation formulation with enhanced acid protection for oral delivery of Salmonella phages using polymers. This was [...] Read more.

Bacteriophage therapy can successfully provide additional treatment to control Salmonella infection, but low gastric pH limits its oral application. The present study aimed to develop an improved encapsulation formulation with enhanced acid protection for oral delivery of Salmonella phages using polymers. This was achieved by encapsulating a phage cocktail containing three different bacteriophages against Salmonella sp. in alginate beads incorporating polyvinyl alcohol (PVA), PVP-K30, and calcium carbonate as viscosity modifiers and acid protection enhancers. Further, the beads were coated with poly-L-lysine to improve the stability and tested for their efficacy for improved phage viability under in vitro acidic conditions for subsequent use in oral delivery. Moist beads were slimy, and semi-dried beads presented a coarse surface as observed using FE-SEM. In vitro studies revealed that the free phage cocktail exhibited complete inactivation when exposed to acidic pH 2.5 after 15 min incubation. In contrast, the encapsulated phage cocktail showed a decrease of only 1.66 log units in viability when incubated for 90 min at pH 2.5. Furthermore, oral delivery of the encapsulated phage cocktail in the poultry model significantly reduced bacterial load in infected birds’ intestines. Full article

(This article belongs to the Section Bacterial Viruses)

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13 pages, 2486 KB

Open AccessArticle

Identification and Characterization of MmuPV1 Causing Papillomatosis Outbreak in an Animal Research Facility

by Vladimir Majerciak, Kristin E. Killoran, Lulu Yu, Deanna Gotte, Elijah Edmondson, Matthew W. Breed, Renee E. King, Melody E. Roelke-Parker, Paul F. Lambert, Joshua A. Kramer and Zhi-Ming Zheng

Viruses 2025, 17(9), 1204; https://doi.org/10.3390/v17091204 - 1 Sep 2025

Viewed by 493

Abstract

Mouse papillomavirus (MmuPV1) is the first papillomavirus known to infect laboratory mice, making it an irreplaceable tool for research on papillomaviruses. Despite wide use, standardized techniques for conducting MmuPV1 animal research are lacking. In this report, we describe an unexpected MmuPV1 outbreak causing [...] Read more.

Mouse papillomavirus (MmuPV1) is the first papillomavirus known to infect laboratory mice, making it an irreplaceable tool for research on papillomaviruses. Despite wide use, standardized techniques for conducting MmuPV1 animal research are lacking. In this report, we describe an unexpected MmuPV1 outbreak causing recurrent papillomatosis in a specific pathogen-free animal research facility. The infected mice displayed characteristic papillomatosis lesions from the muzzles, tails, and feet with histological signs including anisocytosis, epithelial dysplasia, and typical koilocytosis. Etiology studies showed that the papilloma tissues exhibited MmuPV1 infection with expression of viral early and late genes detected by RNA-ISH using MmuPV1 antisense probe to viral E6E7 region and antisense probe to viral L1 region. The viral L1 protein was detected by an anti-MmuPV1 L1 antibody. PCR amplification and cloning of the entire viral genome showed that the origin of the outbreak virus, named MmuPV1 Bethesda strain (GenBank Acc. No. PX123224), could be traced to the MmuPV1 virus previously used in studies at the same facility. Our data indicate that MmuPV1 could exist in a contaminated environment for a long period of time, and a standardized international animal protocol discussing how to handle MmuPV1 studies is urgently needed. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 787 KB

Open AccessArticle

Vitamin D Status, CMV Seropositivity, and Viral Cytokine Expression in Pregnancy

by Adalvan D. Martins, Jennifer Woo, Brandi Falley and Juliet V. Spencer

Viruses 2025, 17(9), 1203; https://doi.org/10.3390/v17091203 - 31 Aug 2025

Viewed by 480

Abstract

Cytomegalovirus (CMV) is the leading infectious cause of birth defects and has been linked to increased risk of preterm birth (PTB). CMV establishes lifelong latency and is more prevalent among Black and Hispanic/Latina women, populations already at higher risk for adverse pregnancy outcomes. [...] Read more.

Cytomegalovirus (CMV) is the leading infectious cause of birth defects and has been linked to increased risk of preterm birth (PTB). CMV establishes lifelong latency and is more prevalent among Black and Hispanic/Latina women, populations already at higher risk for adverse pregnancy outcomes. Vitamin D deficiency, also common in these groups, has been linked to impaired immune function and increased susceptibility to infections, including CMV. In this cross–sectional study of 63 pregnant minority women (50 CMV+, 13 CMV−), we evaluated associations among serum 25(OH)D levels, CMV serostatus, and cmvIL–10, the CMV–encoded interleukin–10 homolog that modulates host immune responses. While vitamin D insufficiency and CMV seropositivity were both highly prevalent, we found no statistically significant associations between 25(OH)D levels and CMV serostatus or cmvIL–10 levels. These findings highlight the need for further investigation into how vitamin D deficiency and CMV infection may independently or synergistically contribute to maternal and neonatal health disparities. Full article

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

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12 pages, 1531 KB

Open AccessArticle

Long-Term Genomic Surveillance and Immune Escape of SARS-CoV-2 in the Republic of Korea, with a Focus on JN.1-Derived Variants

by Il-Hwan Kim, Eun Ju Lee, Jin Sun No, Ji Yeong Noh, Chae Young Lee, Sang Won O, Yong Jun Choi, Jeong-Ah Kim, Bo Min An, Jeong-Hyun Nam, Jeong-Min Kim, Jee Eun Rhee and Eun-Jin Kim

Viruses 2025, 17(9), 1202; https://doi.org/10.3390/v17091202 - 31 Aug 2025

Viewed by 530

Abstract

Since the onset of the COVID-19 pandemic, the Republic of Korea has experienced continuous waves of SARS-CoV-2 variants. The current study aimed to analyze the long-term trends of variant prevalence and associated changes in immune responses within the country. Whole-genome sequencing was performed [...] Read more.

Since the onset of the COVID-19 pandemic, the Republic of Korea has experienced continuous waves of SARS-CoV-2 variants. The current study aimed to analyze the long-term trends of variant prevalence and associated changes in immune responses within the country. Whole-genome sequencing was performed on confirmed patient samples collected from December 2020 to May 2025, and variant distribution, genetic diversity, and neutralization were compared. As a result of analyzing a total of 157,962 gene sequences, various Omicron sub-lineages, including BA.1, BA.2, BA.5, followed by JN.1, KP.3, and NB.1.8.1, were seen to circulate sequentially over time. The nucleotide diversity of the SARS-CoV-2 genome gradually increased after the JN.1 outbreak. Of the tested variants, hamster antiserum neutralization analysis indicated that Omicron NB.1.8.1, which began to circulate in 2025, exhibited the lowest neutralization activity, with an approximately 6.6-fold decrease compared to JN.1. This suggests a potential expansion in the dominance of new variants with enhanced immune evasion. As the transmission of SARS-CoV-2 continues, new variants with novel characteristics may emerge; therefore, continuous national genomic surveillance and immunological characterization are considered crucial for early detection of emerging variants and for guiding effective public health responses. Full article

(This article belongs to the Section Coronaviruses)

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35 pages, 654 KB

Open AccessArticle

Time Series Analysis of Dengue, Zika, and Chikungunya in Ecuador: Emergence Patterns, Epidemiological Interactions, and Climate-Driven Dynamics (1988–2024)

by José Daniel Sánchez, Carolina Álvarez Ramírez, Emilio Cevallos Carrillo, Juan Arias Salazar and César Barros Cevallos

Viruses 2025, 17(9), 1201; https://doi.org/10.3390/v17091201 - 31 Aug 2025

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Abstract

Background: Ecuador presents a unique epidemiological laboratory for studying arboviral dynamics due to its diverse ecological zones and exposure to climatic variability. Methods: We conducted a comprehensive 36-year analysis (1988–2024) of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) using national surveillance data from [...] Read more.

Background: Ecuador presents a unique epidemiological laboratory for studying arboviral dynamics due to its diverse ecological zones and exposure to climatic variability. Methods: We conducted a comprehensive 36-year analysis (1988–2024) of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) using national surveillance data from Ecuador’s Ministry of Public Health. Statistical analyses included time series decomposition, change-point detection, correlation analysis, and climate association studies. Results: Ecuador reported 387,543 arboviral cases, with dengue comprising 91.3% (353,782 cases). Dengue exhibited endemic–epidemic cycles with major peaks during El Niño events (1994: 10,247 cases; 2000: 22,937 cases; 2015: 42,483 cases; 2024: 23,156 cases through week 26). CHIKV emerged explosively in 2015 (29,124 cases, incidence 181.10 per 100,000), followed by ZIKV in 2016 (2947 cases). Both showed rapid decline post-epidemic. Severe dengue cases paradoxically decreased from 2–4% of total cases in early 2000s to <0.1% post-2016, suggesting immunological modulation. Cross-correlation analysis revealed significant associations between climatic indices and epidemic timing (

r = 0.67

,

p < 0.001

), particularly for the El Niño-Southern Oscillation. Conclusions: Arboviral diseases in Ecuador function as an integrated epidemiological system with evidence of viral interactions, cross-protective immunity, and strong climate forcing. These findings emphasize the need for integrated surveillance and adaptive control strategies. Full article

(This article belongs to the Special Issue Preparation for the Next Potential Pandemic—Chikungunya, Dengue, Zika and Other Viruses)

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18 pages, 20579 KB

Open AccessArticle

Isolation and Characterization of a Novel Porcine Teschovirus 2 Strain: Incomplete PERK-Mediated Unfolded Protein Response Supports Viral Replication

by Xiaoying Feng, Yiyang Du, Yueqing Lv, Xiaofang Wei, Chang Cui, Yibin Qin, Bingxia Lu, Zhongwei Chen, Kang Ouyang, Ying Chen, Zuzhang Wei, Weijian Huang, Ying He and Yifeng Qin

Viruses 2025, 17(9), 1200; https://doi.org/10.3390/v17091200 - 31 Aug 2025

Viewed by 452

Abstract

Porcine Teschovirus (PTV) is a highly prevalent pathogen within swine populations, primarily associated with encephalitis, diarrhea, pneumonia, and reproductive disorders in pigs, thereby posing a significant threat to the sustainable development of the pig farming industry. In this study, a novel strain of [...] Read more.

Porcine Teschovirus (PTV) is a highly prevalent pathogen within swine populations, primarily associated with encephalitis, diarrhea, pneumonia, and reproductive disorders in pigs, thereby posing a significant threat to the sustainable development of the pig farming industry. In this study, a novel strain of PTV was isolated from the feces of a pig exhibiting symptoms of diarrhea, utilizing PK-15 cell lines. The structural integrity of the viral particles was confirmed via transmission electron microscopy, and the viral growth kinetics and characteristics were evaluated in PK-15 cells. High-throughput sequencing facilitated the acquisition of the complete viral genome, and subsequent phylogenetic analysis and full-genome alignment identified the strain as belonging to the PTV 2 genotype. Further investigation revealed that infection with the PTV-GXLZ2024 strain induces phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α) in PK-15 cells, indicating activation of the unfolded protein response (UPR) through the PERK pathway, with minimal involvement of the IRE1 or ATF6 pathways. Notably, ATF4 protein expression was progressively downregulated throughout the infection, while downstream CHOP protein levels remained unchanged, indicating an incomplete UPR induced by PTV-GXLZ2024. Furthermore, PERK knockdown was found to enhance the replication of PTV-GXLZ2024. This study provides critical insights into the molecular mechanisms underlying PTV pathogenesis and establishes a foundation for future research into its evolutionary dynamics and interactions with host organisms. Full article

(This article belongs to the Section Animal Viruses)

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17 pages, 1782 KB

Open AccessArticle

Protein Language Models Expose Viral Immune Mimicry

by Dan Ofer and Michal Linial

Viruses 2025, 17(9), 1199; https://doi.org/10.3390/v17091199 - 31 Aug 2025

Viewed by 627

Abstract

Viruses have evolved sophisticated solutions to evade host immunity. One of the most pervasive strategies is molecular mimicry, whereby viruses imitate the molecular and biophysical features of their hosts. This mimicry poses significant challenges for immune recognition, therapeutic targeting, and vaccine development. In [...] Read more.

Viruses have evolved sophisticated solutions to evade host immunity. One of the most pervasive strategies is molecular mimicry, whereby viruses imitate the molecular and biophysical features of their hosts. This mimicry poses significant challenges for immune recognition, therapeutic targeting, and vaccine development. In this study, we leverage pretrained protein language models (PLMs) to distinguish between viral and human proteins. Our model enables the identification and interpretation of viral proteins that most frequently elude classification. We characterize these by integrating PLMs with explainable models. Our approach achieves state-of-the-art performance with ROC-AUC of 99.7%. The 3.9% of misclassified sequences are signified by viral proteins with low immunogenicity. These errors disproportionately involve human-specific viral families associated with chronic infections and immune evasion, suggesting that both the immune system and machine learning models are confounded by overlapping biophysical signals. By coupling PLMs with explainable AI techniques, our work advances computational virology and offers mechanistic insights into viral immune escape. These findings carry implications for the rational design of vaccines, and improved strategies to counteract viral persistence and pathogenicity. Full article

(This article belongs to the Special Issue Herpesviruses and Associated Diseases)

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26 pages, 1977 KB

Open AccessArticle

Whole-Exome Sequencing Reveals Rare Genetic Variants in Saudi COVID-19 Patients with Extreme Phenotypes

by Rashid Mir, Mohammad Fahad Ullah, Imadeldin Elfaki, Mohammad A. Alanazi, Naseh A. Algehainy, Faisal H. Altemani, Mamdoh S. Moawadh, Faris J. Tayeb, Badr A. Alsayed, Mohammad Muzaffar Mir, Jaber Alfaifi, Syed Khalid Mustafa, Jameel Barnawi and Salma Saleh Alrdahe

Viruses 2025, 17(9), 1198; https://doi.org/10.3390/v17091198 - 30 Aug 2025

Viewed by 489

Abstract

The global impact of COVID-19 was staggering, with millions of cases and related mortality reported worldwide. Genetic variations play a significant role in determining an individual’s susceptibility to SARS-CoV-2 infection and progress to severe disease. This pilot study provides an experimental approach using [...] Read more.

The global impact of COVID-19 was staggering, with millions of cases and related mortality reported worldwide. Genetic variations play a significant role in determining an individual’s susceptibility to SARS-CoV-2 infection and progress to severe disease. This pilot study provides an experimental approach using WES to identify certain rare and novel genetic variants that might affect an individual’s susceptibility to the risk of SARS-CoV-2 infection, offering an initial exploration of these genetic variants. In the study cohort with 16 patients, the mortality rate was higher in male patients due to severe disease. There was a substantial burden of comorbidity, including hypertension, ischemic heart disease, and T2DM, conditions which independently increase the risk of adverse outcomes in COVID-19 patients. A total of 4478 variants were identified, distributed across 322 genes within the cohort. The majority of these variants were missense substitutions along with frameshift variants, inframe insertions/deletions (indels), and nonsense variants. The variants were further categorized by types to include single-nucleotide polymorphisms (SNPs), deletions (DEL), and insertions (INS). The gene with the highest number of variants was HLA-DRB1, followed by HLA-B, ABO, HPS4, and SP110 displaying both common polymorphisms and rare variants. Moreover, the HLA-B gene exhibited the highest number of rare candidate variants, followed by AK2, IRF7, KMT2D, TAP1, and HLA-DRB1. Several genes harbored multiple novel variants, including TAP1, AK2, G6PC3, HLA-B, IL12RB2, and ITGB2. The frequencies of the identified variants were found to be either zero or extremely low (below 1% threshold) in the Middle Eastern or in the overall combined population, suggesting that these are indeed rare and do not represent common indigenous polymorphisms. Functional enrichment analysis of the constructed protein–protein interaction network in our preliminary findings revealed that the identified genes are primarily enriched in pathways associated with immune deficiency and DNA repair. This initial exploration of genetic variants in COVID-19 susceptibility provides a foundation for future large-scale studies. Full article

(This article belongs to the Section Coronaviruses)

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