Viruses

14 pages, 3092 KB

Open AccessArticle

An RNAi Therapy That Attenuates Multi-Organ Viremia and Improves Animal Survival in a Lethal EMCV Challenge Model

by Yaxin Zhang, Jiayu Yue, Bei Wu, Jingying Xie, Jiying Xu, Wenqing Gao, Ruofei Feng and Adi Idris

Viruses 2025, 17(9), 1240; https://doi.org/10.3390/v17091240 (registering DOI) - 14 Sep 2025

Abstract

Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen that infects many animals with mild symptoms. However, swine is the most receptive host and causes acute and lethal myocarditis and/or encephalitis, and induces sudden death in piglets. There are currently no approved antivirals against [...] Read more.

Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen that infects many animals with mild symptoms. However, swine is the most receptive host and causes acute and lethal myocarditis and/or encephalitis, and induces sudden death in piglets. There are currently no approved antivirals against EMCV. In recent years, antiviral therapies based on small interfering RNA (siRNA) have been rapidly developed as effective alternative therapies. In this study, we designed siRNAs targeting highly conserved regions in the EMCV genome coinciding with VP2 and 3C genes. We show that these siRNAs were non-immunostimulatory and significantly inhibited EMCV replication in vitro. The siRNAs were then complexed in liposomes before testing in a lethal EMCV mouse model in vivo. Both prophylactic and therapeutic intravenous delivery of siRNAs ameliorated viral infection in multiple organs and improved animal survival. This is the first demonstration of the use of a liposomal delivery platform to deliver highly conserved anti-EMCV siRNAs for EMCV antiviral therapy in vivo. Full article

(This article belongs to the Special Issue Antiviral Development for Emerging and Re-Emerging Viruses)

12 pages, 708 KB

Open AccessArticle

Long-Term Nutritional Deficits and Growth Patterns in Children with Congenital Zika Virus Syndrome: Evidence from a Brazilian Cohort

by Carolina Santos Souza Tavares, Raquel Souza Marques, Janiele de Sá Ferreira, Marcela Barros Barbosa de Oliveira, Monique Carla da Silva Reis and Paulo Ricardo Martins-Filho

Viruses 2025, 17(9), 1239; https://doi.org/10.3390/v17091239 (registering DOI) - 14 Sep 2025

Abstract

Children with Congenital Zika Virus Syndrome (CZVS) experience severe neurological and nutritional impairments. Although immediate clinical consequences are well-documented, long-term anthropometric and nutritional outcomes remain poorly understood. This study assessed longitudinal anthropometric and nutritional outcomes in children affected by CZVS. A cohort of [...] Read more.

Children with Congenital Zika Virus Syndrome (CZVS) experience severe neurological and nutritional impairments. Although immediate clinical consequences are well-documented, long-term anthropometric and nutritional outcomes remain poorly understood. This study assessed longitudinal anthropometric and nutritional outcomes in children affected by CZVS. A cohort of 38 children aged ≥ 5 years diagnosed with CZVS was followed at a reference center in Northeast Brazil. Anthropometric measures (weight, height, BMI, head circumference) were collected using standardized methods, including digital scales and anthropometric tape measures. Growth was analyzed using WHO Anthro and WHO Anthro Plus software (version 3.2.2). Dietary intake was evaluated through two 24 h recalls and analyzed with NutWIN 2.5 software. Nutritional status was classified using WHO growth standards, and associations between dietary intake and BMI were statistically examined. Children showed significant linear growth improvement (p = 0.007) without corresponding weight gain, leading to worsening BMI classifications (p = 0.017). Dietary evaluations revealed limited dietary diversity, frequent intake of ultra-processed foods, inadequate fruit consumption, and widespread insufficiencies in caloric and micronutrient intake (zinc, calcium, iron, vitamin D). Low carbohydrate intake was significantly associated with inadequate BMI (p = 0.030). Multidisciplinary nutritional interventions addressing medical, dietary, educational, and socioeconomic factors are essential for improving health outcomes in children with CZVS. Full article

(This article belongs to the Special Issue Zika Virus and Congenital Zika Syndrome, 2nd Edition)

► Show Figures

Figure 1

23 pages, 4392 KB

Open AccessArticle

Integrative Mechanistic Studies Identify Reticulon-3 as a Critical Modulator of Infectious Exosome-Driven Dengue Pathogenesis

by Razieh Bitazar, Clinton Njinju Asaba, Saina Shegefti, Tatiana Noumi, Julien Van Grevenynghe, Salim T. Islam, Patrick Labonté and Terence Ndonyi Bukong

Viruses 2025, 17(9), 1238; https://doi.org/10.3390/v17091238 (registering DOI) - 13 Sep 2025

Abstract

The dengue virus (DENV) exploits host cell exosome pathways to disseminate and evade immunity. However, the host factors enabling this process remain poorly defined. Here, we demonstrate that DENV infection robustly induces expression of the short isoform of Reticulon 3 (RTN3S) in hepatic [...] Read more.

The dengue virus (DENV) exploits host cell exosome pathways to disseminate and evade immunity. However, the host factors enabling this process remain poorly defined. Here, we demonstrate that DENV infection robustly induces expression of the short isoform of Reticulon 3 (RTN3S) in hepatic (Huh7) and monocytic cells, and that RTN3S is a critical driver of infectious exosome biogenesis. RTN3S physically associates with double-stranded viral RNA and the DENV non-structural protein 3 (NS3) in infected cells, indicating its integration into the viral replication complex. Loss of RTN3 markedly reduced exosome production and the exosomal export of viral RNA and proteins, demonstrating that RTN3S is required for efficient exosome-mediated viral release. Conversely, overexpression of full-length RTN3S dramatically increased the release of infectious virus-containing exosomes; truncation of the RTN3S C-terminal domain abolished this enhancement, confirming the essential role of the C-terminus in RTN3S’s pro-viral exosomal function. In DENV-infected monocytes, we observed a shift toward a CD16-positive intermediate phenotype, accompanied by the upregulation of genes involved in vesicle biogenesis and stress response. These infected monocytes also secreted higher levels of inflammatory cytokines. Similarly, monocytes from Dengue patients exhibited high RTN3 expression, which correlated with an expansion of intermediate (CD16⁺) subsets and enriched expression of vesicle trafficking machinery genes. These findings reveal a previously unrecognized mechanism by which DENV hijacks RTN3S to promote the formation of infectious exosomes, thereby facilitating viral dissemination and immune evasion. RTN3S thus represents a novel element of the Dengue pathogenesis and a potential target for host-directed antiviral strategies. Full article

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

17 pages, 1098 KB

Open AccessArticle

Immunogenicity and Safety Results of a Randomized, Three-Arm, Phase IV Clinical Trial of Concomitant Administration of Typhoid Vi Conjugate Vaccine with Measles and Rubella Vaccine in Healthy Infants

by Songa Narayana Rao, Deepali Ambike, Mahantesh Patil, Sanjay Vasant Mankar, Nishant Verma, Neeta Hanumante, Lisa Sarangi, Monjori Mitra, Godatwar Preeti, Bhaskar Jedhe Deshmukh, Girish Nanoti, Mohammad Moonis Akbar Faridi, Pavankumar Daultani, Ravindra Mittal, Kapil Maithal, Kevinkumar Kansagra, Deven V. Parmar, Radhakrishnan Kunnathamman, Manickam Elaiyaraja, Trayambak Dutta, Manish Mahajan and Samir Desai Show full author list Hide full author list

Viruses 2025, 17(9), 1237; https://doi.org/10.3390/v17091237 - 12 Sep 2025

Viewed by 69

Abstract

Typhoid fever, measles, and rubella continue to contribute significantly to childhood morbidity and mortality in India. In line with WHO recommendations for co-administration of Typhoid Conjugate Vaccine (TCV) and measles–rubella (MR) vaccine at 9 months of age, this phase IV, randomized, open-label, multicenter [...] Read more.

Typhoid fever, measles, and rubella continue to contribute significantly to childhood morbidity and mortality in India. In line with WHO recommendations for co-administration of Typhoid Conjugate Vaccine (TCV) and measles–rubella (MR) vaccine at 9 months of age, this phase IV, randomized, open-label, multicenter clinical trial was conducted to assess their immunological compatibility and safety when administered concomitantly. A total of 900 healthy Indian infants aged 9–10 months were randomized into three groups: Group A received TCV and MR vaccine concomitantly; Group B received MR on Day 0 and TCV on Day 28; Group C received TCV on Day 0 and MR on Day 28. Subjects were followed for 6 months after concomitant/last vaccination. Seroconversion rates (SC) in Groups A/B/C at Day 28 were 90.2%/75.3%/89.5% for anti-Vi; 80.4%/75.2%/77.7% for anti-measles, and 87.7%/84.0%/85.2% for anti-rubella antibodies. By study end, SC for anti-Vi was 87.1%/71.6%/83.0%, while SC for anti-measles and anti-rubella reached ~90% and ≥98%, respectively, across all groups. Geometric mean titers increased significantly for all antigens, with no evidence of immunological interference. Safety assessments showed adverse events in 23.9%/32.0%/32.7% participants in Group A/B/C. Most adverse events were mild, and only one serious adverse event was reported. These findings support the co-administration of TCV and MR vaccine as a safe and effective strategy. Full article

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

► Show Figures

Figure 1

16 pages, 921 KB

Open AccessArticle

Viral Burden of Respiratory Syncytial Virus and Viral Coinfections as Factors Regulating Paediatric Disease Severity

by Velia Chiara Di Maio, Rossana Scutari, Martina Mastropaolo, Luna Colagrossi, Giulia Linardos, Luana Coltella, Stefania Ranno, Eugenia Galeno, Mara Pisani, Anna Chiara Vittucci, Sebastian Cristaldi, Massimiliano Raponi, Alberto Villani, Cristina Russo and Carlo Federico Perno

Viruses 2025, 17(9), 1236; https://doi.org/10.3390/v17091236 - 11 Sep 2025

Viewed by 104

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections (ARIs) in children. However, the clinical impact of RSV co-infection with other respiratory viruses remains unclear. This study investigates the frequency and clinical outcomes of RSV infections in a large [...] Read more.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections (ARIs) in children. However, the clinical impact of RSV co-infection with other respiratory viruses remains unclear. This study investigates the frequency and clinical outcomes of RSV infections in a large paediatric cohort. Methods: Paediatric patients with RSV-positive respiratory samples admitted to Bambino Gesù Children’s Hospital between January 2022 and April 2024 were analysed. Results: Within 17,259 respiratory samples from 9877 paediatric patients, 952 (9.6%) were RSV-positive. Among these, 637 patients with ARI were included. RSV affected the lower respiratory tract in 549 cases (86.2%) and the upper tract in 88 (13.8%) cases. RSV mono-infection was found in 286 (44.9%) patients, while 351 (55.1%) patients had co-infections. Mono-infections showed lower cycle-threshold (CT) than co-infections in both upper and lower tract (p-value:0.002 and 0.037, respectively). Pneumonia was associated with RSV co-infection (N = 48, 15.4%), whereas bronchiolitis was mostly seen in mono-infection (N = 196, 78.1%, p-value:0.002). Regression analysis showed an association between pneumonia and co-infection (AOR: 1.97 [1.06–3.64], p-value = 0.031), higher CT (AOR [95% CI]: 1.07 [1.02–1.11], p-value = 0.006) and older age (AOR [95% CI]: 1.48 [1.31–1.68], p-value < 0.001), whereas bronchiolitis was associated with mono-infection, younger age and lower CT. Conclusions: This study highlights the role of RSV in paediatric disease and emphasises the importance of early diagnosis, personalised treatment and preventive strategies to improve outcomes and reduce the burden of disease. Full article

(This article belongs to the Special Issue Influenza and Other Respiratory Viruses: Prevention, Diagnosis, Treatment: 2nd Edition)

► Show Figures

Figure 1

13 pages, 277 KB

Open AccessBrief Report

Tick-Borne Encephalitis Serological Survey of Students from University of Liège

by Claude Saegerman, Constance Wielick, Gilles Darcis, Nicole Maréchal, Fabrice Bureau, Laurent Gillet, Anne-Françoise Donneau, Kevin K. Ariën and Marjan Van Esbroeck

Viruses 2025, 17(9), 1235; https://doi.org/10.3390/v17091235 - 11 Sep 2025

Viewed by 159

Abstract

Background: Zoonotic risks in exposed students are poorly documented in Belgium. According to the literature, even though human tick-borne encephalitis (TBE) infection risk has increased significantly in southern Belgium, no previous human serological survey has demonstrated specific antibodies directed at TBE virus. Methods [...] Read more.

Background: Zoonotic risks in exposed students are poorly documented in Belgium. According to the literature, even though human tick-borne encephalitis (TBE) infection risk has increased significantly in southern Belgium, no previous human serological survey has demonstrated specific antibodies directed at TBE virus. Methods and principal findings: The aim of this paper was to perform a representative serological survey on sera involving students at the University of Liege, in the southern part of Belgium, to discover possible exposure to TBEV. A total of 207 sera samples were randomly chosen and analyzed using ELISA IgM (with 1 positive student out of 207) and ELISA IgG (with 10 positive students out of 207), subsequent serial immunofluorescence antibody testing (IFAT) IgG (with 8 positive students out of 10 positive in ELISA IgG) and serial IFAT IgM (with 1 negative student out of 1 positive in ELISA IgM), and confirmatory tests, i.e., 50% and 90% plaque reduction neutralization tests (PRNTs) (1 strongly positive student out of 8 positive in IFAT). Conclusions and significance: The exposure of students from the southern part of Belgium (area with increasing risk) to TBEV was assessed for the first time. Antibodies against TBEV could only be demonstrated in 1 out of 207 students. This finding contributes to better decision-making in public health and prevention and management of tick-borne diseases in the context of climate change. Awareness among all students should be prioritized, with prevention measures against tick bites, particularly during forest and recreational activities contributing to risk, to maintain the current low seroprevalence levels. Full article

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

19 pages, 2974 KB

Open AccessArticle

Detection and Genetic Characterization of Red-Spotted Grouper Nervous Necrosis Virus and a Novel Genotype of Nervous Necrosis Virus in Black Sea Bass from the U.S. Atlantic Coast

by Jan Lovy, Miriam Abbadi, Anna Toffan, Nilanjana Das, James N. Neugebauer, William N. Batts and Peter J. Clarke

Viruses 2025, 17(9), 1234; https://doi.org/10.3390/v17091234 - 10 Sep 2025

Viewed by 224

Abstract

Nervous necrosis virus (NNV) causes a neurologic disease in a wide range of marine fish and poses serious disease risks to marine aquaculture worldwide. Little is known about the presence of NNV along the Atlantic coast of the United States, aside from the [...] Read more.

Nervous necrosis virus (NNV) causes a neurologic disease in a wide range of marine fish and poses serious disease risks to marine aquaculture worldwide. Little is known about the presence of NNV along the Atlantic coast of the United States, aside from the presence of barfin flounder nervous necrosis virus (BFNNV) in coldwater species in the northern part of this range. Herein we conducted surveillance for NNV from 2020 to 2022 in the mid-Atlantic region of the United States in black sea bass Centropristis striata, a serranid fish that is found throughout the eastern U.S. coast. Molecular detection methods have identified and characterized red-spotted grouper nervous necrosis virus (RGNNV) sequences at low prevalence throughout the years. Further, in 2022, a higher prevalence of a novel NNV genotype, tentatively named black sea bass nervous necrosis virus (BSBNNV), was characterized for the first time. Though virus isolation was unsuccessful, this study was the first to genetically identify NNV in this region and in this species. These findings highlight the need for further research on NNV to understand epidemiology and virulence in the context of marine fisheries and an emerging marine aquaculture industry in the United States. Full article

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

► Show Figures

Figure 1

19 pages, 6504 KB

Open AccessArticle

CLEC5A Activation in Inflammatory Monocytes: A Mechanism for Enhanced Adaptive Immunity Following COVID-19 mRNA Vaccination in a Preclinical Study

by Renan Galuzo, Thiago Lazari Machado, Ryann de Souza Nascimento, Jorvan Ramos de Medeiros, Luciana Neves Tubarão, Jane Silva, Vanessa Pimenta Rocha, Tamiris Azamor, Felipe Soares Coelho, Andrea Marques Vieira da Silva, Lorenna Carvalho da Rosa, Juliana Fernandes Amorim da Silva, Renata Tourinho Santos, Rodrigo Müller, Carolina Baeta Salvador Várady, Ana Paula Dinis Ano Bom, Patricia Cristina da Costa Neves and Juliana Gil Melgaço

Viruses 2025, 17(9), 1233; https://doi.org/10.3390/v17091233 - 10 Sep 2025

Viewed by 214

Abstract

Background: CLEC5A is a C-type lectin expressed by monocytes and neutrophils, playing an important role in innate immunity. Although it has been shown to interact with the spike protein of SARS-CoV-2, its role during vaccination remains poorly understood. Methods: To address this question, [...] Read more.

Background: CLEC5A is a C-type lectin expressed by monocytes and neutrophils, playing an important role in innate immunity. Although it has been shown to interact with the spike protein of SARS-CoV-2, its role during vaccination remains poorly understood. Methods: To address this question, we combined in vitro assays to characterize CLEC5A and spike expression and their impact on monocyte differentiation and T-cell activation; in vivo studies to evaluate CLEC5A expression, immune responses, and vaccine efficacy in a murine model; and in silico analyses to identify potential spike epitopes and CLEC5A interaction sites. Results: The Pfizer-BioNTech bivalent mRNA vaccine induced spike expression and CLEC5A upregulation in THP-1 monocytes, promoting M1-like differentiation and CD86⁺ activation. In PBMC co-cultures, CLEC5A⁺ monocytes acted as antigen-presenting cells, releasing inflammatory chemokines and activating both CD4⁺ and CD8⁺ T cells, thereby linking CLEC5A expression to adaptive immunity. In mice, CLEC5A expression was observed on inflammatory monocytes (CCR2⁺CX3CR1^low) within two days of vaccination. In vivo, CLEC5A expression increased during SARS-CoV-2 infection and after immunization, but declined following viral challenge in vaccinated animals. Consistently, robust humoral and cellular responses were detected post-immunization. In silico analysis further suggested differential CLEC5A binding across B- and T-cell epitopes within the spike glycoprotein. Conclusions: These findings suggest that CLEC5A may play a role in bridging innate and adaptive immune responses during SARS-CoV-2 vaccination. Although further studies with different vaccine platforms are necessary to confirm and expand these observations, our results provide preliminary evidence supporting the potential of CLEC5A as an exploratory biomarker of vaccine-induced immunity. Full article

(This article belongs to the Section Coronaviruses)

► Show Figures

Graphical abstract

14 pages, 819 KB

Open AccessArticle

Neurocognitive Impairment in ART-Experienced People Living with HIV: An Analysis of Clinical Risk Factors, Injection Drug Use, and the sCD163

by Syed Zaryab Ahmed, Faiq Amin, Nida Farooqui, Zhannur Omarova, Syed Faisal Mahmood, Qurat ul ain Khan, Haider A. Naqvi, Aida Mumtaz, Saeeda Baig, Muhammad Rehan Khan, Sharaf A. Shah, Ali Hassan, Srinivasa Bolla, Shamim Mushtaq and Syed Hani Abidi

Viruses 2025, 17(9), 1232; https://doi.org/10.3390/v17091232 - 10 Sep 2025

Viewed by 177

Abstract

Background: In people living with HIV (PLHIV), ongoing neuronal injury has shown a correlation with elevated levels of soluble markers of immune activation, such as sCD163. Additionally, various risk factors, such as injection drug use (IDU), can independently affect immune and cognitive functions, [...] Read more.

Background: In people living with HIV (PLHIV), ongoing neuronal injury has shown a correlation with elevated levels of soluble markers of immune activation, such as sCD163. Additionally, various risk factors, such as injection drug use (IDU), can independently affect immune and cognitive functions, leading to neurocognitive impairment (NCI). However, the potential sCD163-IDU-NCI axis in ART-experienced PLHIV is not clear. This study aims to determine NCI prevalence and investigate the interplay between risk factors and sCD163 in Pakistani PLHIV. Methods: For this cross-sectional study, 150 PLHIV and 30 HIV-negative people who inject drugs (PWID) were recruited using a convenience sampling strategy. NCI screening was performed using the International HIV Dementia Scale (IHDS) tool. Blood samples from PLHIV were used to perform HIV recency testing using the Asante Rapid Recency Assay, and to evaluate sCD163 levels using ELISA. Sociodemographic and clinical data were collected from medical records. Subsequently, descriptive statistics were used to summarize data variables, while comparisons (two and multiple groups) between participants with and without NCI were conducted, respectively, using the Mann–Whitney test or Kruskal–Wallis test for continuous variables, and Fisher’s exact test for categorial variables. Receiver Operating Characteristic (ROC) curve analysis was performed to assess the discriminative ability of sCD163. Logistic regression was used to identify predictors of neurocognitive impairment. Results: The majority of PLHIV had IDU as a high-risk behavior. In PLHIV, the median age was 34.5 years (IQR: 30–41), ART duration was 35 months (IQR: 17–54), and median CD4 count was 326.5 cells/µL (IQR: 116–545.5). Long-term infections (>6 months post-seroconversion; median ART duration: 35 months; median CD4 counts: 326.5 cells/μL) were noted in 83.3% of PLHIV. IHDS-based screening showed that 83.33% (all PLHIV) and 50% (PLHIV with no IDU history) scored ≤ 9 on the IHDS, suggestive of NCI. IHDS-component analysis showed the memory recall to be significantly affected in PLHIV compared to controls (median score 3.2 versus 3.7, respectively, p < 0.001). Regression analysis showed only long-term infection (OR: 2.99, p = 0.03) to be significantly associated with neurocognitive impairment. sCD163 levels were significantly lower in PLHIV with NCI (mean = 7.48 ng/mL, SD = 7.05) compared to those without NCI (mean = 14.82 ng/mL, SD = 8.23; p < 0.0001), with an AUC of 0.803 (95% CI: 0.72–0.88). However, after adjusting for IDU history, the regression analysis showed an odds ratio for sCD163 of 0.998 (95% CI: 0.934, 1.067, p = 0.957), indicating no association between sCD163 levels and NCI. Conclusion: This study reports a high prevalence of NCI in Pakistani PLHIV, and no association between sCD163 and neurocognitive impairment in PLHIV after adjustment for a history of IDU. Long-term infection and IDU were significantly linked to NCI, while only IDU was associated with lower sCD163 levels, regardless of NCI. Full article

(This article belongs to the Special Issue HIV Neurological Disorders: 2nd Edition)

► Show Figures

Figure 1

21 pages, 294 KB

Open AccessArticle

Susceptibility and Transmission Dynamics of Peste des Petits Ruminants Virus in Domestic and Wild Ruminants: Experimental Insights from Kazakhstan

by Lespek Kutumbetov, Balzhan Myrzakhmetova, Aiganym Tussipova, Gulzhan Zhapparova, Karina Bissenbayeva, Talshyngul Tlenchiyeva, Sergazy Nurabayev, Aslan Kerimbayev, Mukhit Orynbayev, Edil Makhashov and Kuandyk Zhugunissov

Viruses 2025, 17(9), 1231; https://doi.org/10.3390/v17091231 - 9 Sep 2025

Viewed by 313

Abstract

Peste des petits ruminants (PPR) is an extremely contagious viral disease that significantly affects the health of small ruminants and the economies of livestock, particularly in areas adjacent to endemic regions. This study focused on assessing the vulnerability of different domestic and wild [...] Read more.

Peste des petits ruminants (PPR) is an extremely contagious viral disease that significantly affects the health of small ruminants and the economies of livestock, particularly in areas adjacent to endemic regions. This study focused on assessing the vulnerability of different domestic and wild animal species in Kazakhstan, which includes local sheep and goats, African Cameroon goats, saigas, calves, and ground squirrels, to infection by the PPR virus (PPRV). Experimental infections used a virulent strain of PPRV (Nigeria 76/1), with animals being monitored over a period of 21–28 days to evaluate clinical signs, pathological lesions, and viral dissemination. The manifestation of disease differed across species, breed, and age. In Cameroon, goats and saigas displayed severe illness with a mortality rate of 100% and elevated virus levels in key organs, whereas local sheep and goats presented age-related subacute, abortive, and latent manifestations. Calves exhibited mild, subclinical infections, while ground squirrels showed no susceptibility. Viral shedding was observed in the secretions of infected animals, with transmission occurring through airborne and alimentary pathways. No virus carriage was detected in the animals that had recovered. The investigation emphasizes the notable variations in PPRV pathogenesis and transmission risk among different species, highlighting the necessity for focused surveillance and control strategies to avert incursions in PPR-free areas like Kazakhstan. Full article

(This article belongs to the Section Animal Viruses)

18 pages, 2165 KB

Open AccessArticle

Genomic Analysis of Rotavirus G8P[8] Strains Detected in the United States Through Active Surveillance, 2016–2017

by Mary C. Casey-Moore, Mathew D. Esona, Slavica Mijatovic-Rustempasic, Jose Jaimes, Rashi Gautam, Mary E. Wikswo, John V. Williams, Natasha Halasa, James D. Chappell, Daniel C. Payne, Mary Allen Staat, Geoffrey A. Weinberg and Michael D. Bowen

Viruses 2025, 17(9), 1230; https://doi.org/10.3390/v17091230 - 9 Sep 2025

Viewed by 314

Abstract

G8 rotaviruses are primarily associated with animals and infrequently cause infections in humans. The first detection of G8 strains in humans occurred around 1979, and since then, their presence has been sporadic, particularly in the United States (U.S.). During the 2016–2017 rotavirus surveillance [...] Read more.

G8 rotaviruses are primarily associated with animals and infrequently cause infections in humans. The first detection of G8 strains in humans occurred around 1979, and since then, their presence has been sporadic, particularly in the United States (U.S.). During the 2016–2017 rotavirus surveillance season, the New Vaccine Surveillance Network (NVSN) identified 36 G8P[8] rotavirus strains across four sites in the U.S. This study presents the whole-genome characterization of these G8P[8] strains, along with comparative sequence analyses against the current vaccine strains, Rotarix and RotaTeq. Each strain exhibited a DS-1-like backbone with a consensus genotype constellation of G8P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 and exhibited high genetic similarities to G8P[8] strains previously detected in Europe and Asia. Clinical analysis revealed no significant differences in hospitalization rates, length of stay, or severity scores between G8P[8] RVA-positive and non-G8P[8] RVA-positive subjects. Additionally, phylodynamic analysis determined the evolutionary rates and the most recent common ancestor for these strains, highlighting the importance of ongoing monitoring of rotavirus genotypes to assess the spread of these emerging G8P[8] strains. Full article

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

► Show Figures

Figure 1

13 pages, 6946 KB

Open AccessArticle

Camelpox Virus in Western Kazakhstan: Isolation and Phylogenetic Analysis of a New Strain

by Yerbol Bulatov, Nurlan Kozhabergenov, Zhanat Amanova, Zhanna Sametova, Zhanat Kondybaeva, Ruslan Abitayev, Abdurakhman Ussembay, Alina Kurmasheva, Dariya Toktyrova, Dana Mazbayeva, Kuandyk Zhugunissov, Muratbay Mambetaliyev, Bekbolat Usserbayev and Sholpan Turyskeldy

Viruses 2025, 17(9), 1229; https://doi.org/10.3390/v17091229 - 9 Sep 2025

Viewed by 485

Abstract

This study continues earlier work aimed at identifying potential natural reservoirs of camelpox virus (CMLV) during interepizootic periods. In 2023–2024, field expeditions in western Kazakhstan led to the collection and analysis of biological samples from camels, rodents and hematophagous insects. Despite the absence [...] Read more.

This study continues earlier work aimed at identifying potential natural reservoirs of camelpox virus (CMLV) during interepizootic periods. In 2023–2024, field expeditions in western Kazakhstan led to the collection and analysis of biological samples from camels, rodents and hematophagous insects. Despite the absence of clinical symptoms, PCR-positive results were obtained from camel blood samples. These samples underwent molecular genetic analysis, including viral DNA detection and whole-genome sequencing. Using next-generation sequencing, the complete genome of the Camelpox virus/Beineu/2023 isolate (202.273 bp) was obtained and deposited in the NCBI database (accession number PV920573.1). The isolate showed >98% genetic similarity to the previously described Kazakhstan strain M-96, indicating long-term local circulation of a genetically stable variant. Phylogenetic analysis confirmed the isolate’s evolutionary conservatism and close relationship with other CMLV strains. The findings suggest that camels serve as a natural reservoir, enabling viral persistence and potential reactivation under stress-related conditions. The observed geographic clustering underscores the need for region-specific molecular surveillance to ensure timely detection of new variants and prevent cross-border spread. Full article

(This article belongs to the Special Issue Viral Diseases of Domestic Animals)

► Show Figures

Figure 1

3 pages, 164 KB

Open AccessReply

Reply to Saeed et al. 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 Alfredo Caturano, Luca Rinaldi and Antonio Izzi

Viruses 2025, 17(9), 1228; https://doi.org/10.3390/v17091228 - 9 Sep 2025

Viewed by 178

Abstract

We appreciate the thoughtful commentary by Muhammad Hassan Saeed et al [...] Full article

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

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 - 8 Sep 2025

Cited by 1 | Viewed by 305

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, 726 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 - 7 Sep 2025

Viewed by 1270

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)

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 612

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)

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 743

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)

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 496

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))

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 928

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)

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 713

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)

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 448

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)

► Show Figures

Figure 1

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 - 7 Sep 2025

Viewed by 810

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)

► Show Figures

Figure 1

12 pages, 659 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 - 6 Sep 2025

Viewed by 382

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)

► Show Figures

Figure 1

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 - 6 Sep 2025

Viewed by 456

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)

► Show Figures

Figure 1

10 pages, 448 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 - 6 Sep 2025

Viewed by 441

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)

► Show Figures

Figure 1

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

Viewed by 530

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, 3003 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

Viewed by 496

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)

► Show Figures

Figure 1

12 pages, 4871 KB

Open AccessArticle

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

Viewed by 484

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)

► Show Figures

Graphical abstract

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 551

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)

► Show Figures

Figure 1

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 575

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)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Viruses, Volume 17, Issue 9 (September 2025) – 92 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI