Viruses

11 pages, 585 KiB

Open AccessArticle

Characterisation of Orthohantavirus Serotypes in Human Infections in Kazakhstan

by Nur Tukhanova, Anna Shin, Abhishek Bakuli, Lyazzat Yeraliyeva, Nurbek Maikanov, Guenter Froeschl, Zauresh Zhumadilova, Gulnara Tokmurziyeva, Edith Wagner, Sandra Essbauer and Lukas Peintner

Viruses 2025, 17(7), 925; https://doi.org/10.3390/v17070925 (registering DOI) - 28 Jun 2025

Abstract

Orthohantavirus infection is a zoonotic disease transmitted to humans through contact with infected rodents. In Eurasia, Old World Orthohantaviruses can cause haemorrhagic fever with renal syndrome (HFRS), while in the Americas, New World Orthohantaviruses are responsible for hantavirus cardiopulmonary syndrome (HCPS). In Kazakhstan, [...] Read more.

Orthohantavirus infection is a zoonotic disease transmitted to humans through contact with infected rodents. In Eurasia, Old World Orthohantaviruses can cause haemorrhagic fever with renal syndrome (HFRS), while in the Americas, New World Orthohantaviruses are responsible for hantavirus cardiopulmonary syndrome (HCPS). In Kazakhstan, the first recorded cases of HFRS appeared in the West Kazakhstan region in 2000, which has since then been established as an endemic area due to the presence of stable rodent reservoirs and recurring human infections. Routine diagnosis of HFRS in this region relies primarily on immunoassays. To enhance diagnostic precision, we aimed to implement both serological and molecular methods on samples from suspected HFRS cases in the endemic West Kazakhstan region and non-endemic Almaty City. A total of 139 paired serum, saliva, and urine samples were analysed using IgM/IgG ELISA, immunoblot assays, and qPCR. Our findings confirm that suspected HFRS cases in West Kazakhstan are associated with the Puumala virus serotype. Full article

(This article belongs to the Special Issue Hantavirus 2024)

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10 pages, 3437 KiB

Open AccessArticle

Phylogenetic and Mutation Analysis of Hemagglutinin Gene from Highly Pathogenic Avian Influenza Virus H5 Clade 2.3.4.4b in South America

by Alfredo Bruno, Domenica de Mora, Miguel Angel Garcia-Bereguiain and Juan Cristina

Viruses 2025, 17(7), 924; https://doi.org/10.3390/v17070924 (registering DOI) - 28 Jun 2025

Abstract

The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America. The introduction of the virus into South [...] Read more.

The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America. The introduction of the virus into South America was reported for the first time in Colombia in October 2022, followed by outbreaks in other South American countries affecting poultry, wild birds, mammals, and humans. In this study, a phylogenetic and mutation analysis of the hemagglutinin (HA) gene of HPAIV H5N1 2.3.4.4b viruses isolated in South America was performed to analyze its evolution and its transmission and zoonotic potential. The analysis shows an increase in the viral effective population size between April and June 2022, which was followed by multiple outbreaks of HPAIV H5N1 clade 2.3.4.4b in South America. Moreover, the virus variants evolved from a recent common ancestor estimated to have existed in June 2017. The mean rate of evolution of the HA gene was 6.95 × 10⁻³ substitutions per site per year, and the sequence analysis of HA identified a mutation (D171N) located at antibody binding sites and viral oligomerization interfaces, with implications for immune response evasion and new host species infection. Additionally, viral strains from South America share the substitutions L104M, T156A, P181S, and V210A, compared to the vaccine strain A/chicken/Ghana/AVL763/2021. Understanding the dynamics of viral evolution and transmission is essential for effective prevention strategies to mitigate future outbreaks. Full article

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

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16 pages, 1889 KiB

Open AccessArticle

Orthoflavivirus omskense NS1 Protein Induces Microvascular Endothelial Permeability In Vitro

by Bogdana I. Kravchuk, Andrey L. Matveev, Andrey A. Kechin, Alena O. Stepanova, Lyudmila A. Emelyanova, Sargis M. Khachatryan, Nina V. Tikunova and Yana A. Khlusevich

Viruses 2025, 17(7), 923; https://doi.org/10.3390/v17070923 (registering DOI) - 28 Jun 2025

Abstract

Orthoflavivirus omskense (Omsk hemorrhagic fever virus, OHFV) is a tick-borne flavivirus that causes Omsk hemorrhagic fever (OHF), a severe zoonotic disease endemic to Western Siberia. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis was investigated and [...] Read more.

Orthoflavivirus omskense (Omsk hemorrhagic fever virus, OHFV) is a tick-borne flavivirus that causes Omsk hemorrhagic fever (OHF), a severe zoonotic disease endemic to Western Siberia. Despite the fact that the role of NS1 proteins of various mosquito-borne flaviviruses in pathogenesis was investigated and their ability to affect human endothelial permeability was shown, the role of the NS1 protein of OHFV in pathogenesis is unstudied. In this work, the ability of OHFV NS1 to induce human endothelial permeability was investigated for the first time. It was shown that recombinant OHFV NS1 produced in eucaryotic cells directly affects both human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC) in vitro. RNAseq of endothelial cells treated with OHFV NS1 indicated that OHFV NS1 enhances the expression of genes associated with cellular stress responses, vascular signaling, and cell–cell junction regulation, resulting in a nonspecific increase in the endothelial permeability of various vessels. These results suggest that the NS1 protein may contribute to OHFV pathogenesis by disrupting endothelial barrier function and promoting vascular leakage, potentially playing a role in the hemorrhagic manifestations of Omsk hemorrhagic fever. Full article

(This article belongs to the Special Issue The Structure and Function of Flavivirus Genes and Proteins)

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22 pages, 3253 KiB

Open AccessArticle

Infections of Aedes Mosquito Cells by Wolbachia Strains wAu and wMelpop Modulate Host Cellular Transcriptomes Differently and Suppress Dengue Viral Replication

by Amber R. Mickelson, Julia Felton, Olivia Cheschi, Emily Spacone, Kaitlyn Connors, Jacob Thornsberry and Tadahisa Teramoto

Viruses 2025, 17(7), 922; https://doi.org/10.3390/v17070922 (registering DOI) - 28 Jun 2025

Abstract

Dengue virus serotypes 1-4 (DENV1-4) have spread through tropical and subtropical countries, causing endemic and epidemic diseases. Recently, a novel field approach using the Wolbachia symbiont was proposed to suppress DENV transmission via the mosquito vectors Aedes aegypti and Aedes albopictus. Previously, [...] Read more.

Dengue virus serotypes 1-4 (DENV1-4) have spread through tropical and subtropical countries, causing endemic and epidemic diseases. Recently, a novel field approach using the Wolbachia symbiont was proposed to suppress DENV transmission via the mosquito vectors Aedes aegypti and Aedes albopictus. Previously, we showed that a Wolbachia strain, wMelPop, suppresses DENV2 replication in the C6/36 albopictus cell line, with the mutant DENV2 appearing and replacing the wild type DENV2. In this study, we expanded the analysis to include replications of all DENV serotypes 1-4, effects of wAu Wolbachia in C6/36 cells, and wMelPop-influences on the Aag2 aegypti cell line. It was revealed that both wAu and wMelPop reduce all DENV infectious titers without dominant appearances of the mutant viruses, despite varied effects on the viral copy numbers. The host transcriptomic profiles by RNA-seq were also variously altered by wAu and wMelPop (ranging from 10 to 30%, Log₂FC > 2 or <−2, p < 0.05). Those transcripts were not further altered by DENV infection. In contrast, abundant transcriptomic alterations by DENV infection in naïve C6/36 and Aag2 cells were blocked by either wAu or wMelPop. These results indicate that Wolbachia prevents host cellular transcriptomic alterations which are induced by DENV infection, affecting the cellular homeostasis necessary for DENV replication. Full article

(This article belongs to the Special Issue The Impact of Wolbachia on Virus Infection)

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18 pages, 2943 KiB

Open AccessArticle

IFI16 Mediates Deacetylation of KSHV Chromatin via Interaction with NuRD and Sin3A Co-Repressor Complexes

by Anandita Ghosh, Bala Chandran and Arunava Roy

Viruses 2025, 17(7), 921; https://doi.org/10.3390/v17070921 (registering DOI) - 28 Jun 2025

Abstract

IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional [...] Read more.

IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal that IFI16 associates with and facilitates the recruitment of the NuRD and Sin3A co-repressor complexes—both multiprotein, HDAC1/2-containing chromatin regulators—on KSHV episomes. Depletion of IFI16 led to reductions in NuRD and Sin3A occupancy on viral chromatin, accompanied by increased histone acetylation at lytic gene promoters. These results suggest that IFI16 plays a critical role in recruiting or stabilizing these HDAC-containing co-repressor complexes on the KSHV genome, thereby enforcing transcriptional silencing of lytic genes and maintaining latency in KSHV. Our study expands the known functions of IFI16 and identifies a novel epigenetic mechanism by which it modulates herpesviral chromatin states. Full article

(This article belongs to the Special Issue Epigenetic Modifications in Viral Infections, Volume II)

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16 pages, 2580 KiB

Open AccessArticle

Complex Medium-Chain Triglycerides Mitigate Porcine Epidemic Diarrhea Virus Infection in Piglets by Enhancing Anti-Inflammation, Antioxidation, and Intestinal Barrier Function

by Tingting Hu, Yunhao Liu, Sihui Gao, Xiaonan Zhao, Huangzuo Cheng, Youjun Hu, Huaqiao Tang, Zhiwen Xu and Chunlin Fang

Viruses 2025, 17(7), 920; https://doi.org/10.3390/v17070920 (registering DOI) - 27 Jun 2025

Abstract

Porcine epidemic diarrhea (PED), a highly contagious enteric disease caused by the porcine epidemic diarrhea virus (PEDV), is characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and significant economic losses in the swine industry. The shortage of effective [...] Read more.

Porcine epidemic diarrhea (PED), a highly contagious enteric disease caused by the porcine epidemic diarrhea virus (PEDV), is characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and significant economic losses in the swine industry. The shortage of effective PED vaccines emphasizes the need to explore potent natural compounds for therapeutic intervention. It has been shown that glycerol monolaurate (GML) effectively inhibits PEDV replication in vivo and in vitro. Further investigation is needed to assess whether complex medium-chain triglycerides (CMCTs), composed of glyceryl tricaprylate/caprate (GTCC) and GML, offer an efficient anti-PEDV activity. In this study, piglets were orally infected with PEDV and exhibited typical clinical signs, including diarrhea and vomiting, accompanied by intestinal inflammation, oxidative stress, and tissue damage. CMCTs were administered orally twice daily for one week. In vivo findings indicate that CMCT treatment alleviated clinical signs and prevented weight loss. It significantly increased serum immunoglobulins (IgG, IgM, and IgA) and intestinal mucosal sIgA and MUC-2 levels, while reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-17) and increasing antiviral interferons (IFN-α and IFN-γ), anti-inflammatory cytokines (IL-4 and IL-10), and IL-22. Antioxidant enzyme activities (T-AOC, SOD, GSH-Px, and CAT) were elevated, whereas oxidative stress markers (iNOS, NO, and MDA) were decreased. Expression of intestinal tight junction proteins claudin-1 and ZO-1 was restored. Moreover, CD4⁺ and CD8⁺ T cell populations increased, and the functions of regulatory T cells (Tregs) were restored. Gut microbiota analysis showed increased beneficial genera (Streptococcus and Ligilactobacillus) and decreased pathogenic Escherichia-Shigella. These results demonstrate that CMCTs mitigate PEDV infection by enhancing anti-inflammation, antioxidation, and intestinal barrier function, as well as modulating gut microbiota composition. This study improves the understanding of the pathogenesis of PEDV and highlights CMCTs as a promising therapeutic candidate for PED. Full article

(This article belongs to the Section Animal Viruses)

21 pages, 1884 KiB

Open AccessReview

Potential Resistance Mechanisms Exhibited by Cystic Fibrosis Patients Against SARS-CoV-2

by Yasmin K. Elsharabassi, Nuha T. Swaidan and Mohamed M. Emara

Viruses 2025, 17(7), 919; https://doi.org/10.3390/v17070919 (registering DOI) - 27 Jun 2025

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease pandemic. The virus primarily spreads through person-to-person contact via aerosols and droplets, contributing to high case numbers and related morbidities. SARS-CoV-2 targets the respiratory tract, causing acute [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease pandemic. The virus primarily spreads through person-to-person contact via aerosols and droplets, contributing to high case numbers and related morbidities. SARS-CoV-2 targets the respiratory tract, causing acute respiratory distress syndrome, particularly in immunocompromised individuals such as those with cystic fibrosis (CF). CF is a life-threatening genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to impaired respiratory function and recurrent severe respiratory symptoms. Despite their potential vulnerability, CF patients have shown a lower incidence of severe COVID-19, suggesting protective factors against SARS-CoV-2. Differential expression of the ACE2 receptor, crucial for viral entry, and other host factors, such as TMPRSS2, may play a role in this resistance to SARS-CoV-2. Analyzing the genomics and transcriptomics profiles of CF patients could provide insights into potential resistance mechanisms. The potential resistance mechanisms include blood and extracellular ATP levels, a deleted/dysfunctional CFTR gene, ACE and ACE2 regulation and expression, ACE and ACE2 polymorphism effects, host proteins and SARS-CoV-2 interactions, and SMN1 and ACE/ACE2 interactions. This review discusses the underlying factors and potential resistance mechanisms contributing to CF patients’ responses to SARS-CoV-2 infection. The review provides an opportunity to further investigate future therapy and research through understanding the underlying potential resistance mechanisms exhibited by CF patients against SARS-CoV-2, including ACE and ACE2 polymorphisms. Full article

(This article belongs to the Section Coronaviruses)

27 pages, 4730 KiB

Open AccessArticle

Genetic and Immunological Profiling of Recent SARS-CoV-2 Omicron Subvariants: Insights into Immune Evasion and Infectivity in Monoinfections and Coinfections

by Nadine Alvarez, Irene Gonzalez-Jimenez, Risha Rasheed, Kira Goldgirsh, Steven Park and David S. Perlin

Viruses 2025, 17(7), 918; https://doi.org/10.3390/v17070918 (registering DOI) - 27 Jun 2025

Abstract

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact on public health continue to demand attention as the virus continues to evolve, demonstrating a remarkable ability to adapt to diverse selective pressures including immune responses, therapeutic treatments, and [...] Read more.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact on public health continue to demand attention as the virus continues to evolve, demonstrating a remarkable ability to adapt to diverse selective pressures including immune responses, therapeutic treatments, and prophylactic interventions. The SARS-CoV-2 variant landscape remains dynamic, with new subvariants continuously emerging, many harboring spike protein mutations linked to immune evasion. In this study, we characterized a panel of live SARS-CoV-2 strains, including those key subvariants implicated in recent waves of infection. Our findings revealed a significant variability in mutation patterns in the spike protein across the strains analyzed. Commercial antibodies and human convalescent plasma (HCoP) samples from unvaccinated donors were ineffective in neutralizing the most recent Omicron subvariants, particularly after the emergence of JN.1 subvariant. Using human airway epithelial cells derived from healthy bronchiolar tissue (hBAEC), we established both monoinfections and coinfections involving SARS-CoV-2, Influenza A virus H1N1 (IFAV_H1N1) and Respiratory Syncytial Virus (RSV). Assessments were conducted to compare viral infectivity and the production and release of immune mediators in the apical and basolateral compartments. Notably, Omicron KP.3.1.1 subvariant induced a more pronounced cytopathic effect in hBAEC compared to its parental strain JN.1 and even surpassed the impact observed with the ancestral wild-type virus (WA1/2020, Washington strain). Furthermore, the coinfection of KP.3.1.1 subvariant with IFAV_H1N1 or RSV did not attenuate SARS-CoV-2 infectivity; instead, it significantly exacerbated the pathogenic synergy in the lung epithelium. Our study demonstrated that pro-inflammatory cytokines IL-6, IFN-β, and IL-10 were upregulated in hBAEC following SARS-CoV-2 monoinfection with recent Omicron subvariants as well as during coinfection with IFAV_H1N1 and RSV. Taken together, our findings offer new insights into the immune evasion strategies and pathogenic potential of evolving SARS-CoV-2 Omicron subvariants, as well as their interactions with other respiratory viruses, carrying important implications for therapeutic development and public health preparedness. Full article

(This article belongs to the Special Issue COVID-19 Complications and Co-infections)

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36 pages, 1423 KiB

Open AccessReview

Baculoviruses as Microbial Pesticides: Potential, Challenges, and Market Overview

by Maider Martínez-Balerdi, Javier Caballero, Eduardo Aguirre, Primitivo Caballero and Inés Beperet

Viruses 2025, 17(7), 917; https://doi.org/10.3390/v17070917 (registering DOI) - 27 Jun 2025

Abstract

Baculoviruses represent a promising group of microbial insecticides for the biological control of agricultural pests, particularly those within the order Lepidoptera. Their high host specificity and environmental safety make them ideal candidates for inclusion in integrated pest management (IPM) programs. This review presents [...] Read more.

Baculoviruses represent a promising group of microbial insecticides for the biological control of agricultural pests, particularly those within the order Lepidoptera. Their high host specificity and environmental safety make them ideal candidates for inclusion in integrated pest management (IPM) programs. This review presents a comprehensive overview of baculovirus biology, highlighting their infection mechanisms, selectivity, and ecological compatibility. Special attention is given to advances in mass production systems—both in vivo and in vitro—and formulation technologies that improve field efficacy and environmental persistence, including UV protectants and microencapsulation. Regulatory aspects are also discussed, comparing international approval pathways and highlighting the disparity between regions with supportive policies (e.g., Latin America, Asia) and those with more restrictive frameworks (e.g., the European Union). Additionally, the current global market landscape for baculovirus-based products is examined, with emphasis on recent growth, commercialized formulations, and challenges such as host resistance and the limited spectrum of action. By synthesizing findings from the scientific literature and industry reports, this review underscores the role of baculoviruses as effective, sustainable alternatives or complements to chemical insecticides in modern agriculture, contributing to the reduction in pesticide residues and environmental impact. Full article

(This article belongs to the Special Issue Insect Viruses and Pest Management, the Third Edition)

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15 pages, 1524 KiB

Open AccessArticle

Phloroglucinol Oligomers from Callistemon rigidus as Novel Anti-Hantavirus Replication Agents

by Jin-Xuan Yang, E-E Luo, Yue-Chun Wu, Kai Zhao, Wei Hou, Mu-Yuan Yu, Xu-Jie Qin and Xing-Lou Yang

Viruses 2025, 17(7), 916; https://doi.org/10.3390/v17070916 (registering DOI) - 27 Jun 2025

Abstract

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees [...] Read more.

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from Callistemon rigidus leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics. Full article

(This article belongs to the Special Issue Hantavirus 2024)

16 pages, 2309 KiB

Open AccessArticle

Immune and Safety Analysis of ultraIPV^TM, a Novel UVC-Inactivated Polio Vaccine

by David A. MacLeod, John K. Tobin, Ruth V. Bushnell, Taralyn J. Wiggins, Shyamkumar TS, Ramchander Nadipelly, Steven Lawson, Viju V. Pillai, Gregory J. Tobin and Stephen J. Dollery

Viruses 2025, 17(7), 915; https://doi.org/10.3390/v17070915 (registering DOI) - 27 Jun 2025

Abstract

The eradication of poliovirus remains a global health priority, with inactivated polio vaccines (IPVs) playing a pivotal role in immunization strategies. Over the past decades, advancements in IPV production have focused on optimizing safety, efficacy, and immunogenicity while addressing vaccine production and logistical [...] Read more.

The eradication of poliovirus remains a global health priority, with inactivated polio vaccines (IPVs) playing a pivotal role in immunization strategies. Over the past decades, advancements in IPV production have focused on optimizing safety, efficacy, and immunogenicity while addressing vaccine production and logistical challenges. This paper discusses a novel IPV candidate, ultraIPV^TM, which departs from conventional formalin inactivation and uses a modern ultraviolet C (UVC) inactivation technology that includes a powerful antioxidant that protects virus epitopes from damage during and after irradiation. The potential of UVC inactivation to maintain structural integrity and immunogenicity of viral antigens, while circumventing safety issues with conventional vaccines, could bolster global polio eradication efforts and holds promise for applications to numerous other viral pathogens. Wistar rats were immunized with three dosages of ultraIPV^TM, IPOL^R, or vehicle alone. Immune responses were analyzed by whole-virus ELISA and antiviral neutralizing responses. Toxicity was analyzed primarily by increases in body weight and cytokine ELISA. Tolerability was analyzed by gross pathological and histological examinations. ultraIPV^TM was determined to be immunogenic and non-toxic. No pathological or histological abnormalities related to the vaccine were observed. The data suggest that ultraIPV^TM is immunogenic and well-tolerated in rats. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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18 pages, 1104 KiB

Open AccessSystematic Review

Current Trends of Human Adenovirus Types Among Hospitalized Children—A Systematic Review

by Janina Soler Wenglein, Luca Scarsella, Christine Kotlewski, Albert Heim and Malik Aydin

Viruses 2025, 17(7), 914; https://doi.org/10.3390/v17070914 (registering DOI) - 27 Jun 2025

Abstract

Human adenoviruses (HAdVs) are pathogens causing different illnesses, particularly in pediatric and immunocompromised patients in developed countries. The clinical spectrum of HAdV-infections ranges from mild to severe, and the clinical presentation varies widely. Certain HAdVs types, including types B3, E4, B7, B14, B21, [...] Read more.

Human adenoviruses (HAdVs) are pathogens causing different illnesses, particularly in pediatric and immunocompromised patients in developed countries. The clinical spectrum of HAdV-infections ranges from mild to severe, and the clinical presentation varies widely. Certain HAdVs types, including types B3, E4, B7, B14, B21, G55, and B66, may be associated with lower respiratory tract infections and thus lead to higher hospitalization, increased morbidity, as well as lethality rates. The aim of this article is to synthesize and analyze the prevalence of specific HAdV types in pediatric patients worldwide. A systematic literature search was performed using MEDLINE, Scopus, and Web of Science. In total, n = 1167 titles and abstracts were screened, and 105 full-text articles were assessed for eligibility. Screening, data extraction, and appraisal were analyzed by reviewers, in accordance with PRISMA guidelines and JBI recommendations. We included studies reporting on currently circulating HAdV types (n = 16). Based on a systematic and narrative approach, relevant types of HAdV biology and infections in children are presented. In detail, HAdV-B3 and HAdV-B7 were commonly associated with severe respiratory tract infections, while HAdV-F40 and HAdV-F41 caused acute gastroenteritis. Moreover, detailed research revealed the critical role of HAdV-C2 and the necessity for particular attention to HAdVs in acute neurological infections. This comprehensive analysis highlights the significant global distribution and diverse clinical implications of different HAdV types in children, pointing out the need for continued surveillance to better understand HAdVs epidemiology and its implications for public health, and future preventive measures, in particular among vulnerable patients. Full article

(This article belongs to the Special Issue Research and Clinical Application of Adenovirus (AdV), 3rd Edition)

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10 pages, 1453 KiB

Open AccessArticle

Measles Sequencing: Lessons Learned from a Large-Scale Outbreak

by Victoria Indenbaum, Efrat Bucris, Keren Friedman, Tatyana Kushnir, Hagar Eliyahu, Roberto Azar, Tal Levin, Yara Kanaaneh, Eric J. Haas, Shepherd Roee Singer, Yaniv Lustig, Ella Mendelson, Oran Erster and Neta S. Zuckerman

Viruses 2025, 17(7), 913; https://doi.org/10.3390/v17070913 (registering DOI) - 27 Jun 2025

Abstract

Between 2018 and 2019, Israel experienced one of its largest measles outbreaks in recent decades, with over 4300 reported cases and more than 100 documented importation events. Despite high national vaccination coverage, the prolonged nature of the outbreak posed a risk to the [...] Read more.

Between 2018 and 2019, Israel experienced one of its largest measles outbreaks in recent decades, with over 4300 reported cases and more than 100 documented importation events. Despite high national vaccination coverage, the prolonged nature of the outbreak posed a risk to the country’s measles elimination status. Traditional epidemiological investigations and genotyping based on the N450 region lacked sufficient resolution to differentiate between sustained local transmission and multiple independent introductions. To address this, we performed whole-genome sequencing on 123 measles virus samples representing both imported and locally acquired cases from diverse geographic regions. Phylogenetic analysis revealed multiple, distinct transmission chains, several of which could be linked to separate importation events. The MF non-coding region (MF-NCR) not only showed the highest genetic variability, but also contained many of the phylogenetic cluster-defining mutations, though informative changes were found throughout the whole genome. These findings demonstrate the value of whole-genome sequencing in resolving complex transmission dynamics and highlight the importance of integrating genomic epidemiology into routine measles surveillance. Such integration can enhance outbreak investigations and better inform public health responses to protect elimination status. Full article

(This article belongs to the Special Issue Measles, Mumps, and Rubella)

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17 pages, 4006 KiB

Open AccessArticle

Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection

by Duo Xu, Mahamaya Biswal, Quanqing Zhang, Christine Light, Yijie Wu, Chenjin Ye, Luis Martínez-Sobrido, Jikui Song and Rong Hai

Viruses 2025, 17(7), 912; https://doi.org/10.3390/v17070912 (registering DOI) - 27 Jun 2025

Abstract

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed unprecedented challenges to public health and economic stability. Central to SARS-CoV-2 pathogenesis is its ability to evade the host immune response by hijacking host pathways via the interaction between [...] Read more.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed unprecedented challenges to public health and economic stability. Central to SARS-CoV-2 pathogenesis is its ability to evade the host immune response by hijacking host pathways via the interaction between viral and host proteins. We identified Ras-GTPase-activating protein SH3 domain-binding protein 1/2 (G3BP1/G3BP2) as a critical host factor that interacts with the viral nucleocapsid (N) protein, emerging from a comparative analysis of proteomic data from multiple studies. We revisited the underlying molecular mechanisms by confirming the residues required for the interaction between G3BP1/G3BP2 and SARS-CoV-2 N protein and showed that this interaction disrupts stress granule formation. Intriguingly, we observed that the ablation of both G3BP1 and G3BP2 enhanced SARS-CoV-2 replication. Our data collectively supports the notion that G3BP1 and G3BP2 play a critical role in modulating the host–virus interface during SARS-CoV-2 infection, and that their multifaceted function in cellular defense extends beyond the stress granule pathway. Full article

(This article belongs to the Special Issue Viral Mechanisms of Immune Evasion)

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21 pages, 568 KiB

Open AccessReview

Armed Phages: A New Weapon in the Battle Against Antimicrobial Resistance

by Cleo Anastassopoulou, Deny Tsakri, Antonios-Periklis Panagiotopoulos, Chrysa Saldari, Antonia P. Sagona and Athanasios Tsakris

Viruses 2025, 17(7), 911; https://doi.org/10.3390/v17070911 (registering DOI) - 27 Jun 2025

Abstract

The increasing prevalence of multidrug-resistant (MDR) bacterial infections necessitates the exploration of alternative antimicrobial strategies, with phage therapy emerging as a viable option. However, the effectiveness of naturally occurring phages can be significantly limited by bacterial defense systems that include adsorption blocking, restriction–modification, [...] Read more.

The increasing prevalence of multidrug-resistant (MDR) bacterial infections necessitates the exploration of alternative antimicrobial strategies, with phage therapy emerging as a viable option. However, the effectiveness of naturally occurring phages can be significantly limited by bacterial defense systems that include adsorption blocking, restriction–modification, CRISPR-Cas immunity, abortive infection, and NAD+ depletion defense systems. This review examines these bacterial defenses and their implications for phage therapy, while highlighting the potential of phages’ bioengineering to overcome these barriers. By leveraging synthetic biology, genetically engineered phages can be tailored to evade bacterial immunity through such modifications as receptor-binding protein engineering, anti-CRISPR gene incorporation, methylation pattern alterations, and enzymatic degradation of bacterial protective barriers. “Armed phages”, enhanced with antimicrobial peptides, CRISPR-based genome-editing tools, or immune-modulating factors, offer a novel therapeutic avenue. Clinical trials of bioengineered phages, currently SNIPR001 and LBP-EC01, showcase their potential to safely and effectively combat MDR infections. SNIPR001 has completed a Phase I clinical trial evaluating safety in healthy volunteers, while LBP-EC01 is in Phase II trials assessing its performance in the treatment of Escherichia coli-induced urinary tract infections in patients with a history of drug-resistant infections. As “armed phages” progress toward clinical application, they hold great promise for precision-targeted antimicrobial therapies and represent a critical innovation in addressing the global antibiotic resistance crisis. Full article

(This article belongs to the Collection Phage Therapy)

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15 pages, 802 KiB

Open AccessArticle

Plant Lectin, MoMo30, Pressures HIV-1 to Select for Variants with Deleted N-Linked Glycosylation Sites

by Morgan I. Coleman, Mahfuz B. Khan, Erick Gbodossou, Amad Diop, Kenya DeBarros, Vincent C. Bond, Virginia Floyd, Kofi Kondwani, Valerie Montgomery Rice and Michael D. Powell

Viruses 2025, 17(7), 910; https://doi.org/10.3390/v17070910 (registering DOI) - 27 Jun 2025

Abstract

Momordica balsamina, a plant traditionally used in African medicine, contains a 30 kDa protein, MoMo30, previously identified by our group as an anti-HIV agent that binds glycan residues on the gp120 envelope protein, thereby acting as an entry inhibitor. In this study, we [...] Read more.

Momordica balsamina, a plant traditionally used in African medicine, contains a 30 kDa protein, MoMo30, previously identified by our group as an anti-HIV agent that binds glycan residues on the gp120 envelope protein, thereby acting as an entry inhibitor. In this study, we investigated whether prolonged exposure to MoMo30 exerts selective pressure on HIV-1 and induces mutations in the viral envelope (env) gene. T-lymphocyte cells were infected with HIV-1_NL4-3 and continuously treated with MoMo30 over a 24-day period. Viral RNA was isolated at regular intervals, and env genes were sequenced using the Illumina platform. RNA sequence variant calling was performed using iVar, which uses a frequency-based binomial test with a default allele frequency threshold of 3% and a minimum base quality of 20 and applies Bonferroni correction for multiple testing. The infectivity of the MoMo30-exposed virus was assessed using MAGI-CXCR4 cells, visualized by β-galactosidase staining, and compared to untreated controls. Statistical significance was determined via two-way ANOVA. MoMo30-treated HIV-1 exhibited multiple detrimental mutations in gp120 and gp41, including missense, nonsense, and frameshift changes. Notably, 32% of N-linked glycosylation sites were deleted in the treated virus, while no such changes were observed in controls. Functionally, the MoMo30-treated virus demonstrated a sixfold reduction in infectivity compared to untreated HIV-1_NL4-3. These findings suggest that MoMo30 imposes genetic pressure on HIV-1_NL4-3, selecting for mutations that reduce viral fitness. Full article

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

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11 pages, 4443 KiB

Open AccessCommunication

Population Genetic Structure of Citrus Tatter Leaf Virus in Zhejiang Province, China

by Lianming Lu, Shunmin Liu, Zhanxu Pu, Baoju An, Danchao Du, Xiurong Hu, Jia Lv and Zhendong Huang

Viruses 2025, 17(7), 909; https://doi.org/10.3390/v17070909 (registering DOI) - 27 Jun 2025

Abstract

Citrus tatter leaf virus (CTLV), a major pathogen threatening global citrus production, remains poorly characterized in terms of its regional genetic diversity and evolutionary dynamics. To address this gap, we conducted a comprehensive population genetic analysis of CTLV in Zhejiang Province, China, using [...] Read more.

Citrus tatter leaf virus (CTLV), a major pathogen threatening global citrus production, remains poorly characterized in terms of its regional genetic diversity and evolutionary dynamics. To address this gap, we conducted a comprehensive population genetic analysis of CTLV in Zhejiang Province, China, using 181 coat protein (CP) gene sequences—the largest regional CTLV dataset to date. Our analyses uncovered substantial genetic diversity among Zhejiang CTLV isolates. Phylogenetic reconstructions revealed that these isolates span multiple clades, closely aligning with global CTLV population structures, indicative of recurrent viral introductions and extensive regional circulation. Population structure analyses revealed significant genetic differentiation driven by geography, with Jinhua isolates forming a distinct cluster, and by host species, with Citrus reticulata ‘Criton’ isolates diverging from those in other citrus varieties. Selection pressure analysis indicated that while most CP polymorphic sites were under purifying selection, several clade-specific codons showed signatures of positive selection. These results offer new insights into CTLV’s population structure and localized evolutionary trajectories, enhancing our understanding of its regional adaptation and informing strategies for disease management and control of this globally significant pathogen. Full article

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

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16 pages, 1446 KiB

Open AccessReview

Emerging Arthropod-Borne Viruses Hijack the Host Cell Cytoskeleton During Neuroinvasion

by Flora De Conto

Viruses 2025, 17(7), 908; https://doi.org/10.3390/v17070908 (registering DOI) - 26 Jun 2025

Abstract

Arthropod-borne viral infections, ranging from asymptomatic to fatal diseases, are expanding from endemic to nonendemic areas. Climate change, deforestation, and globalization favor their spread. Although arboviral manifestations mainly determine the onset of generalized symptoms, distinct clinical signs have been assessed, depending on the [...] Read more.

Arthropod-borne viral infections, ranging from asymptomatic to fatal diseases, are expanding from endemic to nonendemic areas. Climate change, deforestation, and globalization favor their spread. Although arboviral manifestations mainly determine the onset of generalized symptoms, distinct clinical signs have been assessed, depending on the particular arthropod-borne virus (arbovirus) involved in the infectious process. A number of arboviruses cause neuroinvasive diseases in vertebrate hosts, with acute to chronic outcomes. Long-term neurological sequelae can include cognitive dysfunction and Parkinsonism. To increase knowledge of host interactions with arboviruses, in-depth investigations are needed to highlight how arboviruses exploit a host cell for efficient infection and clarify the molecular alterations underlying human brain diseases. This review focuses on the involvement of host cytoskeletal networks and associated signalling pathways in modulating the neurotropism of emerging arboviruses. A better understanding at the molecular level of the potential for emerging infectious diseases is fundamental for prevention and outbreak control. Full article

(This article belongs to the Special Issue Zoonotic and Vector-Borne Viral Diseases)

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31 pages, 3563 KiB

Open AccessArticle

Amino Acid Polymorphisms in the Basic Region of Meq of Vaccine Strain CVI988 Drastically Diminish the Virulence of Marek’s Disease Virus

by Jumpei Sato, Yoshinosuke Motai, Shunsuke Yamagami, Aoi Kurokawa, Shwe Yee Win, Fumiya Horio, Hikaru Saeki, Naoya Maekawa, Tomohiro Okagawa, Satoru Konnai, Kazuhiko Ohashi and Shiro Murata

Viruses 2025, 17(7), 907; https://doi.org/10.3390/v17070907 (registering DOI) - 26 Jun 2025

Abstract

Marek’s disease virus (MDV) is the etiological agent of Marek’s disease (MD), a lymphoproliferative disorder in chickens. Polymorphisms in the MDV-encoded oncoprotein Meq are shared among field strains and correlate with their virulence. The attenuated vaccine strain CVI988 harbors unique amino acid polymorphisms [...] Read more.

Marek’s disease virus (MDV) is the etiological agent of Marek’s disease (MD), a lymphoproliferative disorder in chickens. Polymorphisms in the MDV-encoded oncoprotein Meq are shared among field strains and correlate with their virulence. The attenuated vaccine strain CVI988 harbors unique amino acid polymorphisms in Meq, particularly at positions 71, 77, and 326. In this study, we investigated the impact of these polymorphisms on Meq protein function and MDV virulence. Reporter assays revealed that the substitutions, particularly A71S and K77E, markedly impaired the transcriptional regulatory activity of Meq. To evaluate their effect on virulence, we generated a recombinant MDV based on the very virulent RB-1B strain, encoding Meq with A71S and K77E substitutions (rRB-1B_Meq71/77). Chickens infected with rRB-1B_Meq71/77 developed neither clinical signs nor lymphomas. Flow cytometry revealed no expansion of infected cells in this group, but a marked increase in CD8⁺ T and γδ T cells during early infection. Histopathological analysis also confirmed the absence of MD-associated lesions. These findings demonstrate that the polymorphisms at positions 71 and 77 in the CVI988 strain are sufficient to abolish MDV virulence. This study provides insight into the molecular basis of MDV virulence and informs the strategy for the design of more effective vaccines. Full article

(This article belongs to the Section Animal Viruses)

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