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Viruses
Volume 17
Issue 12
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Viruses, Volume 17, Issue 12 (December 2025) – 119 articles

Cover Story (view full-size image): Chikungunya virus (CHIKV) is a re-emerging alphavirus responsible for outbreaks of acute and chronic arthritic disease worldwide. Despite progress in vaccine development, no licensed CHIKV vaccines or targeted antivirals are currently available. Replication of the CHIKV RNA genome requires the coordinated action of nonstructural proteins, including the RNA-dependent RNA polymerase nsP4, whose regulation remains poorly defined. In this study, we identify a minimal, functional precursor of nsP4 derived from the nsP3–nsP4 polyprotein that supports RNA replication in a cell-based replicon system. Our findings reveal a previously unappreciated role of precursor processing and spatial regulation in polymerase activation and provide a tractable framework for dissecting alphavirus replicase assembly and control. View this paper
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32 pages, 2597 KB  
Article
Modelling the Variability in Immunity Build-Up and Waning Following RNA-Based Vaccination
by Juan Magalang, Tyll Krueger and Joerg Galle
Viruses 2025, 17(12), 1643; https://doi.org/10.3390/v17121643 - 18 Dec 2025
Viewed by 297
Abstract
RNA-based vaccination has been broadly applied in the COVID-19 pandemic. A characteristic of the immunization was fast-waning immunity. However, the time scale of this process varied considerably for virus subtypes and among individuals. Understanding the origin of this variability is crucial in order [...] Read more.
RNA-based vaccination has been broadly applied in the COVID-19 pandemic. A characteristic of the immunization was fast-waning immunity. However, the time scale of this process varied considerably for virus subtypes and among individuals. Understanding the origin of this variability is crucial in order to improve future vaccination strategies. Here, we introduce a mathematical model of RNA-based vaccination and the kinetics of the induced immune response. In the model, antigens produced following vaccination give rise to an immune response leading to germinal center reactions and accordingly B-cell differentiation into memory B-cells and plasma cells. In a negative feedback loop, the antibodies synthesized by newly specified plasma cells shut down the germinal center reaction as well as antigen-induced differentiation of memory B-cell into plasma cells. This limits the build-up of long-lasting immunity and thus is accompanied by fast-waning immunity. The detailed data available on infection with and vaccination against SARS-CoV-2 enabled computational simulation of essential processes of the immune response. Through simulation, we analyzed to what extent a single- or double-dose vaccination provides protection against infection. We find that variability in the immune response in individuals, originating, e.g., in different immune-cell densities, results in a broad log-normal-like distribution of the vaccine-induced protection times that peaks around 100 days. Protection times decrease for virus variants with mutated antibody-binding sites or increased replication rates. Independent of these virus specifics, our simulations suggest optimal timing of a second dose about 5 weeks after the first in agreement with clinical trials. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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10 pages, 459 KB  
Opinion
Europe Faces Multiple Arboviral Threats in 2025
by Yannick Simonin
Viruses 2025, 17(12), 1642; https://doi.org/10.3390/v17121642 - 18 Dec 2025
Viewed by 962
Abstract
The year 2025 likely marks a turning point in both the perception and the reality of mosquito-borne arboviral diseases in Europe. While chikungunya and dengue viruses have long been regarded as tropical illnesses confined to intertropical regions, West Nile virus has circulated for [...] Read more.
The year 2025 likely marks a turning point in both the perception and the reality of mosquito-borne arboviral diseases in Europe. While chikungunya and dengue viruses have long been regarded as tropical illnesses confined to intertropical regions, West Nile virus has circulated for decades in temperate areas, including southern Europe. Nevertheless, all three mosquito-borne viruses are now increasingly established across the European continent. This evolution reflects a profound transformation of the European epidemiological landscape, where arboviral diseases are increasingly emerging as endemic and seasonal threats. This shift concerns not only the scale but also the dynamics of transmission, with the appearance of newly affected regions, an earlier onset of the transmission season, and a broader diversity of arboviruses involved. Europe is thus entering a new phase in which longer, wider, and more intense transmission of vector-borne diseases is likely to become the new norm requiring strengthened preparedness. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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16 pages, 1728 KB  
Article
Phylogeographic and Host Interface Analyses Reveal the Evolutionary Dynamics of SAT3 Foot-And-Mouth Disease Virus
by Shuang Zhang, Jianing Lv, Yao Lin, Rong Chai, Jiaxi Liang, Yan Su, Zhuo Tian, Hanyu Guo, Fuyun Chen, Guanying Ni, Gang Wang, Chunmei Song, Baoping Li, Qiqi Wang, Sen Zhao, Qixin Huang, Xuejun Ji, Jieji Duo, Fengjun Bai, Jin Li, Shuo Chen, Xueying Pan, Qin La, Zhong Hong and Xiaolong Wangadd Show full author list remove Hide full author list
Viruses 2025, 17(12), 1641; https://doi.org/10.3390/v17121641 - 18 Dec 2025
Viewed by 328
Abstract
Foot-and-mouth disease virus (FMDV) serotype SAT3 is a rarely studied serotype primarily circulating in southern Africa, with African buffalo (Syncerus caffer) serving as its key reservoir. In this study, we performed a comprehensive phylogenetic and phylodynamic analysis of SAT3 based on [...] Read more.
Foot-and-mouth disease virus (FMDV) serotype SAT3 is a rarely studied serotype primarily circulating in southern Africa, with African buffalo (Syncerus caffer) serving as its key reservoir. In this study, we performed a comprehensive phylogenetic and phylodynamic analysis of SAT3 based on 81 full-length VP1 gene sequences collected between 1934 and 2018. Maximum likelihood and Bayesian analyses revealed five distinct topotypes, each with clear geographic and host associations. Notably, topotypes I, II and III were observed in both African buffalo and cattle (Bos taurus), while topotype IV appeared restricted to African buffalo. Likelihood mapping indicated moderate to strong phylogenetic signal, and the mean substitution rate was estimated at 3.709 × 10−3 substitutions/site/year under a relaxed molecular clock. The time to the most recent common ancestor (TMRCA) was traced back to 1875. Discrete phylogeographic reconstruction identified Zimbabwe as a major center, with multiple supported cross-border transmission routes. Host transition analysis further confirmed strong directional flow from buffalo to cattle (BF = 1631.09, pp = 1.0), highlighting the wildlife–livestock interface as a key driver of SAT3 persistence. Together, these results underscore the evolutionary complexity of SAT3 and the importance of integrating molecular epidemiology, spatial modeling, and host ecology to inform FMD control strategies in endemic regions. Full article
(This article belongs to the Special Issue Foot-and-Mouth Disease Virus)
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24 pages, 2852 KB  
Review
The Role of Posttranslational Modifications During Ebola Virus Infection
by Joaquin Moreno-Contreras, Yoatzin Peñaflor-Tellez and Ricardo Rajsbaum
Viruses 2025, 17(12), 1640; https://doi.org/10.3390/v17121640 - 18 Dec 2025
Viewed by 541
Abstract
Orthoebolaviruses (OEV) are highly pathogenic viruses responsible for the Ebola virus disease (EVD). To establish a successful infection, OEV hijacks the host cell machinery, which in turn responds to infection by activating cellular antiviral pathways. These processes are regulated via post-translational modifications (PTMs) [...] Read more.
Orthoebolaviruses (OEV) are highly pathogenic viruses responsible for the Ebola virus disease (EVD). To establish a successful infection, OEV hijacks the host cell machinery, which in turn responds to infection by activating cellular antiviral pathways. These processes are regulated via post-translational modifications (PTMs) of both cellular and viral proteins. The most common PTMs include phosphorylation, ubiquitination, acetylation, methylation, and glycosylation. These modifications regulate stability, activity, and interactions between proteins that control the immune response, cell metabolism, and cell death, among others. PTMs are critical during the viral replication cycle as they can be either proviral, facilitating adequate virus replication inside the infected cell, or antiviral, most commonly hindering essential viral processes such as viral genome transcription or replication. Here, we review the different roles of PTMs known to occur during OEV infection in both viral and cellular proteins. Understanding how OEV modulates the fate of host cell proteins through specific PTMs can provide a basis for the development of novel therapeutic strategies. Full article
(This article belongs to the Special Issue 15-Year Anniversary of Viruses)
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19 pages, 1938 KB  
Article
Antiviral and Immunomodulatory Effects of 7-Deaza-2-methyladenosine (7DMA) in a Susceptible Mouse Model of Usutu Virus Infection
by Rebeca P. F. Rocha, Marina A. Fontoura, Fabrício Naciuk, Leonardo C. Oliveira, Alice Nagai, Amanda Bellini Silva, Alexandre Borin, Jaqueline S. Felipe, Marjorie Bruder, Lais D. Coimbra and Rafael Elias Marques
Viruses 2025, 17(12), 1639; https://doi.org/10.3390/v17121639 - 18 Dec 2025
Viewed by 306
Abstract
Usutu virus (USUV) is an emerging arbovirus recently associated with outbreaks in Western Europe. Although USUV is typically associated with asymptomatic or nonspecific febrile disease, the occurrence of severe neuroinvasive forms of disease has raised concern. There is currently no antiviral treatment available [...] Read more.
Usutu virus (USUV) is an emerging arbovirus recently associated with outbreaks in Western Europe. Although USUV is typically associated with asymptomatic or nonspecific febrile disease, the occurrence of severe neuroinvasive forms of disease has raised concern. There is currently no antiviral treatment available for USUV infection; therefore, we sought to investigate the protective effects of the nucleoside analogue 7DMA against USUV. Adding to 7DMA’s activity against USUV in vitro reported by us and others, we found that 7DMA inhibits USUV replication at multiple stages in mammalian cell lines Vero CCL81 and SH-SY5Y. In vivo testing of 7DMA using the susceptible IFNAR-/- mouse model indicated that 7DMA treatment significantly reduced USUV viremia and viral load in tissues and prolonged mice survival. The characterization of the protective effects of 7DMA indicated that treatment also altered immunological aspects of disease development, further increasing the expression of mediators such as CXCL10, IL-15, and IFN-γ, and increasing neutrophil recruitment to target organs. We did not observe significant tissue damage or pathology in USUV-infected mouse brains, suggesting that systemic infection and disease are the major components leading to mortality in this model. We conclude that 7DMA exerts protective effects against USUV infection in the IFNAR-/- model. Full article
(This article belongs to the Special Issue Antiviral Development for Emerging and Re-Emerging Viruses)
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11 pages, 646 KB  
Article
AI-Powered Identification of Human Cell Surface Protein Interactors of the Hemagglutinin Glycoprotein of High-Pandemic-Risk H5N1 Influenza Virus
by Christian Poitras and Benoit Coulombe
Viruses 2025, 17(12), 1638; https://doi.org/10.3390/v17121638 - 17 Dec 2025
Viewed by 333
Abstract
H5N1 is a highly pathogenic avian influenza virus of major global concern. Since 2023, it has circulated widely among wild and farmed birds, with increasing spillover into mammals, including minks, seals, and cattle, and sporadic infections in humans in Chile, the UK, and [...] Read more.
H5N1 is a highly pathogenic avian influenza virus of major global concern. Since 2023, it has circulated widely among wild and farmed birds, with increasing spillover into mammals, including minks, seals, and cattle, and sporadic infections in humans in Chile, the UK, and the USA. The risk of a future pandemic is considered high because ongoing viral evolution could enable efficient human-to-human transmission. The hemagglutinin (HA) glycoprotein is the principal determinant of host range, mediating viral attachment and entry through interactions with sialylated glycans and potentially additional host surface proteins. Here, we developed an artificial intelligence (AI)-based pipeline integrating structural modeling, protein–protein interaction prediction, and biological filtering to identify human cell surface proteins with high likelihood of interacting with H5N1 HA. These interactions may contribute to viral entry and tropism and therefore represent promising candidates for experimental validation and therapeutic targeting. Our findings highlight the utility of AI-driven pipelines in accelerating the discovery of host factors relevant to pandemic influenza viruses. Full article
(This article belongs to the Special Issue Virus-Host Protein Interactions)
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15 pages, 10308 KB  
Article
Quercetin Regulates Autophagy to Inhibit PRRSV Replication Through the PI3K/Akt/mTOR Signaling Pathway
by Yuxin Yang, Xinmiao Li, Haitao Shi, Jiaying Yu, Chen Gao, Yuanhong Liu, Wenjun Feng, Luyuan Peng, Bendong Fu and Pengfei Yi
Viruses 2025, 17(12), 1637; https://doi.org/10.3390/v17121637 - 17 Dec 2025
Viewed by 296
Abstract
Porcine Reproductive and Respiratory Syndrome (PRRS), caused by the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), is a highly contagious viral disease responsible for significant economic losses in the global swine industry. Quercetin, a polyphenolic flavonoid known for its antiviral properties, was investigated [...] Read more.
Porcine Reproductive and Respiratory Syndrome (PRRS), caused by the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), is a highly contagious viral disease responsible for significant economic losses in the global swine industry. Quercetin, a polyphenolic flavonoid known for its antiviral properties, was investigated in this study for its ability to inhibit PRRSV replication by modulating autophagy. Our study demonstrates that quercetin can inhibit PRRSV replication in MARC-45 cells by regulating the degradation of autophagosomes and suppressing the generation of autophagosome. We further suggest that quercetin inhibits PRRSV-induced autophagy via the PI3K/Akt/mTOR signaling pathway, suppressing autophagosome formation while promoting autophagosome-lysosome fusion, ultimately leading to reduced PRRSV replication. In conclusion, our study demonstrates that quercetin inhibits PRRSV replication by regulating autophagy through the PI3K/Akt/mTOR pathway. Full article
(This article belongs to the Section Animal Viruses)
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18 pages, 7065 KB  
Article
Apoptin-Armed Oncolytic Adenovirus Triggers Apoptosis and Inhibits Proliferation, Migration, Invasion, and Stemness of Hepatocellular Carcinoma Hep3B Cells
by Zhaoxing Sun and Wenjie Li
Viruses 2025, 17(12), 1636; https://doi.org/10.3390/v17121636 - 17 Dec 2025
Viewed by 334
Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality, highlighting the urgent need for novel therapeutic strategies. Apoptin, encoded by the VP3 gene of the chicken anemia virus, selectively induces apoptosis in cancer cells while sparing normal cells. We previously engineered a [...] Read more.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality, highlighting the urgent need for novel therapeutic strategies. Apoptin, encoded by the VP3 gene of the chicken anemia virus, selectively induces apoptosis in cancer cells while sparing normal cells. We previously engineered a recombinant oncolytic adenovirus (Ad-VP3) capable of high-level Apoptin expression in tumor cells. In this study, we evaluated the antitumor activity of Ad-VP3 in the human HCC cell line Hep3B. CCK-8, crystal violet, Hoechst 33342 staining, flow cytometry, and tumor sphere formation assays revealed that Ad-VP3 inhibited cell viability, proliferation, and stemness. Annexin V staining, JC-1/TMRM probes, and Western blot analysis demonstrated induction of apoptosis and reduction of mitochondrial membrane potential. Wound-healing, Transwell, and BioCoat invasion assays, along with Western blotting, confirmed suppression of migration and invasion. Ad-VP3 significantly inhibited the viability, proliferation, migration, and invasion of Hep3B cells in a time- and dose-dependent manner. It induced mitochondrial membrane potential loss and apoptosis, downregulated stemness-related proteins (ALDH1A1, KLF4, and Sox2), and suppressed epithelial–mesenchymal transition markers (Snail, Twist1, Slug, Vimentin, and MMP-9), indicating strong antitumor activity. The recombinant oncolytic adenovirus Ad-VP3 exerts potent antitumor effects on hepatocellular carcinoma cells by inducing mitochondrial dysfunctionmediated apoptosis and impairing stemness and metastatic potential, suggesting its promise as a novel therapeutic strategy for HCC. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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18 pages, 1561 KB  
Review
Context-Specific Diversity of Antimicrobial Functions of Interferon-Stimulated Genes
by Munesh K. Harioudh and Saumendra N. Sarkar
Viruses 2025, 17(12), 1635; https://doi.org/10.3390/v17121635 - 17 Dec 2025
Viewed by 448
Abstract
Interferon-stimulated genes (ISGs) were initially discovered for their role in antiviral functions. However, recent studies show evidence of a diverse and context-specific regulatory function of these genes in antiviral and antibacterial protection. The molecular mechanisms of such activities vary depending on the pathogen, [...] Read more.
Interferon-stimulated genes (ISGs) were initially discovered for their role in antiviral functions. However, recent studies show evidence of a diverse and context-specific regulatory function of these genes in antiviral and antibacterial protection. The molecular mechanisms of such activities vary depending on the pathogen, cell type, isoform, and species. In this review, we summarize the context-specific functions of several prominent and well-known ISG families, including OAS, IFITs, ISG15, viperin, ADAR1, and Mx proteins. We provide examples of distinct enzymatic or regulatory mechanisms that are employed by these ISGs to carry out their diverse functions, including nucleic acid sensing, RNA degradation, translation inhibition, membrane remodeling, etc. Full article
(This article belongs to the Special Issue Interferon Signaling in Viral Pathogenesis)
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22 pages, 2099 KB  
Review
The Dual Role of A20 (TNFAIP3) in Viral Infection: A Context-Dependent Regulator of Immunity and Pathogenesis
by Haesung Jeon and Choongho Lee
Viruses 2025, 17(12), 1634; https://doi.org/10.3390/v17121634 - 17 Dec 2025
Viewed by 397
Abstract
A20 (TNFAIP3) is a ubiquitin-editing enzyme that plays a central role in the regulation of inflammation and cell death, primarily through modulation of NF-κB signaling. In the context of viral infection, A20 exhibits a dual nature: it can both suppress antiviral immune responses [...] Read more.
A20 (TNFAIP3) is a ubiquitin-editing enzyme that plays a central role in the regulation of inflammation and cell death, primarily through modulation of NF-κB signaling. In the context of viral infection, A20 exhibits a dual nature: it can both suppress antiviral immune responses to facilitate viral replication and act as a host-protective factor to prevent immunopathology. This review synthesizes current findings on the context-dependent roles of A20, focusing on its capacity to switch between antiviral and proviral functions. We examine how specific determinants—including viral genetic makeup, the infected cell type, and the temporal stage of infection—dictate whether A20 protects the host or facilitates viral persistence. We propose a systematic framework for understanding A20 as a dynamic regulator that orchestrates the balance between pathogen clearance and tissue protection. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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4 pages, 155 KB  
Editorial
Learning from the COVID-19 Pandemic—Through Sharing and Collaboration
by Julian W. Tang
Viruses 2025, 17(12), 1633; https://doi.org/10.3390/v17121633 - 17 Dec 2025
Viewed by 308
Abstract
During the COVID-19 pandemic (which some argue is still ongoing), I led three Special Issues (SIs) that were designed to cover the talking points that arose amongst many practitioners and researchers: (1) How can we maintain our usual diagnostic services in the face [...] Read more.
During the COVID-19 pandemic (which some argue is still ongoing), I led three Special Issues (SIs) that were designed to cover the talking points that arose amongst many practitioners and researchers: (1) How can we maintain our usual diagnostic services in the face of an ongoing pandemic [...] Full article
(This article belongs to the Special Issue Impact of Pandemic Measures on the Epidemiology and Seasonality of Other Viruses)
19 pages, 9776 KB  
Article
Changes in Microbiome Correspond with Diminished Lung Pathophysiology Following Early-Life Respiratory Syncytial Virus Infection or Antibiotic Treatment: Microbiome Following RSV Infection
by Kazuma Yagi, Alexander D. Ethridge, Nobuhiro Asai, Carrie-Anne Malinczak, Llilian Arzola Martinez, Andrew J. Rasky, Susan B. Morris, Nicole R. Falkowski, Wendy Fonseca, Gary B. Huffnagle and Nicholas W. Lukacs
Viruses 2025, 17(12), 1632; https://doi.org/10.3390/v17121632 - 17 Dec 2025
Viewed by 244
Abstract
Early-life respiratory syncytial virus (EL-RSV) infection has been implicated in long-term pulmonary disease in children. In these studies, neonatal BALB/c mice were infected at day 7 of life, leading to >35% losses in critical lung function, airway mucus metaplasia, and transcriptional hallmarks of [...] Read more.
Early-life respiratory syncytial virus (EL-RSV) infection has been implicated in long-term pulmonary disease in children. In these studies, neonatal BALB/c mice were infected at day 7 of life, leading to >35% losses in critical lung function, airway mucus metaplasia, and transcriptional hallmarks of mucus hypersecretion four weeks after RSV infection. While EL-RSV minimally reshaped the resident lung microbiota, it led to significant gut dysbiosis, including a long-term reduction of Proteobacteria that can be a source of protective metabolites related to barrier and immune function. Subsequent studies assessing whether a common infant antibiotic (ampicillin) could mitigate EL-RSV-induced lung alterations revealed further severe gut microbiome alterations and, on its own, later in life, recapitulated the full spectrum of RSV-associated alterations in lung function. Metagenomic inference showed that both RSV and ampicillin administered during early life reduced biosynthetic pathways for microbiome-derived metabolites, which are known to reinforce tight junctions, regulate inflammation, and preserve extracellular matrix elasticity. The shared loss of these metabolic programs provides a mechanistic bridge linking distinct early-life exposures to the microbiome changes and airway mechanical deficits later in life. Collectively, the data suggest that RSV and/or antibiotic-triggered gut dysbiosis is the primary insult that likely promotes improper lung maturation/repair through a metabolite-mediated mechanism and may suggest metabolite restoration as a strategy to promote proper developmental lung function. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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18 pages, 2953 KB  
Article
Evidence from COVID-19 Patients and Murine Studies for a Continuing Trend Towards Targeting of Nasopharyngeal Ciliated Epithelial Cells by SARS-CoV-2 Omicron Sublineages
by Agnes Carolin, Cameron R. Bishop, Kexin Yan, Branka Grubor-Bauk, Mark P. Plummer, Bing Tang, Michael Leitner, Eamon Raith, Simon C. Barry, Christopher M. Hope, Wilson Nguyen, Daniel J. Rawle and Andreas Suhrbier
Viruses 2025, 17(12), 1631; https://doi.org/10.3390/v17121631 - 17 Dec 2025
Viewed by 363
Abstract
We describe RNA-Seq analyses conducted on nasopharyngeal swabs collected from 37 patients admitted to an Australian intensive care unit from October 2022 to August 2023. During this time, the dominant omicron sublineage infections broadly progressed from BA.5 to BA.2-like, to XBB-like, then XBC, [...] Read more.
We describe RNA-Seq analyses conducted on nasopharyngeal swabs collected from 37 patients admitted to an Australian intensive care unit from October 2022 to August 2023. During this time, the dominant omicron sublineage infections broadly progressed from BA.5 to BA.2-like, to XBB-like, then XBC, consistent with global trends. Viral load and patient metadata correlations indicated this cohort was broadly representative of severe COVID-19 patients. Human gene expression analyses were complicated by the large range (>5 log) and variability in viral reads. Nevertheless, the comparison of XBC and BA.5 samples that had comparable viral read counts, revealed differentially expressed genes and a cellular deconvolution signature that indicated increased targeting of ciliated epithelial cells by XBC. To obtain more evidence for increased targeting of ciliated epithelial cells by the later omicron sublineage viruses, a series of mouse strains were infected with a BA.5 or a XBB isolate. Increased infection of the nasal turbinates and ciliated epithelial cells by XBB was demonstrated by viral titrations and immunohistochemistry, respectively. Compared with previous lineages, the omicron lineage showed increased targeting of ciliated epithelia in the upper respiratory tract, with the data presented herein suggesting this trend continued for the omicron sublineages. Full article
(This article belongs to the Section Coronaviruses)
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4 pages, 172 KB  
Editorial
Canine Distemper Virus: Special Issue Editorial
by Mónica G. Candela and Nieves Ortega
Viruses 2025, 17(12), 1630; https://doi.org/10.3390/v17121630 - 17 Dec 2025
Viewed by 325
Abstract
This Special Issue of Viruses focuses on canine distemper virus (CDV) in a context where the disease continues to challenge clinical practice, epidemiology, and wildlife conservation, despite more than half a century of systematic vaccination [...] Full article
(This article belongs to the Special Issue Canine Distemper Virus)
15 pages, 2223 KB  
Article
Cardiac Tissue Damage in a Female Animal Post-COVID Model: Relevance of Chemokine-Mediated Inflammation
by Silvia Flaj-Prados, Esperanza Herradón Pliego, Carlos Goicoechea Garcia, Eva M. Sánchez-Robles, Lars Arendt-Nielsen, César Fernández-de-las-Peñas and Visitación López-Miranda
Viruses 2025, 17(12), 1629; https://doi.org/10.3390/v17121629 - 16 Dec 2025
Viewed by 402
Abstract
Post-COVID cardiac complications have emerged as a significant and persistent clinical concern, yet their underlying mechanisms remain poorly understood. Animal models can act as proxies to investigate the pathophysiology of the human, post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this experimental [...] Read more.
Post-COVID cardiac complications have emerged as a significant and persistent clinical concern, yet their underlying mechanisms remain poorly understood. Animal models can act as proxies to investigate the pathophysiology of the human, post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this experimental study was to evaluate the expression of inflammatory biomarkers in cardiac tissue 28 days after SARS-CoV-2 infection in a female hACE2 mouse model, with a focus on chemokine-mediated immune activation. Twelve female C57BL/6 hACE2 mice were infected with the Omicron variant (BA.1.17 lineage) of SARS-CoV-2, and eleven non-infected mice served as controls. Cardiac tissue was analyzed via Western blot for markers of innate immune activation (TLR4, MyD88, NF-κB) and pro-inflammatory cytokines (IL-6, IL-18, IL-1β, TNF-α, CD11d). Cardiac tissue injury markers (iNOS, PAI-1 and Connexin43) were also analyzed. Compared to non-infected mice, cardiac tissue from infected mice showed significantly higher expression of IL-6 (p = 0.028), indicating an inflammatory state, and CD11d (p = 0.016), suggesting an inflammatory stage accompanied by sustained activation of chemokine-mediated inflammatory signaling. No significant differences in TLR4 (p = 0.340), MyD88 (p = 0.410), NF-κB p65 (p = 0.780), IL-18 (p = 0.548), IL-1β (p = 0.455), and TNF-α (p = 0.125) expressions were observed Similarly, no changes in cardiac damage markers (iNOS: p = 0.4684; PAI-1: p = 0.5345; Connexin 43: p = 0.2879) were found. The results of this experimental study would support the hypothesis of persistent low-grade inflammation as a contributor to post-COVID cardiac sequelae in females that is not accompanied by severe tissue damage, as also observed in clinical studies. This study also reinforces the need for studies evaluating the functional and structural evolution of the myocardium after an acute SARS-CoV-2 infection. Full article
(This article belongs to the Section Coronaviruses)
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26 pages, 3262 KB  
Review
A Review of Receptor Recognition Mechanisms in Coronaviruses
by Jie Liu, Wenjing Luo, Jianming Li, Bingyi Cai, Zhiwei Lei, Shiyun Lin, Zhuohong Chen, Zhaoyang Yue, Xulin Chen, Yongkui Li, Zhen Luo, Qiwei Zhang and Xin Chen
Viruses 2025, 17(12), 1628; https://doi.org/10.3390/v17121628 - 16 Dec 2025
Viewed by 324
Abstract
Cellular receptor recognition exerts fundamental roles during coronavirus infection. Clarifying the regulatory mechanism of virus receptor helps to better understand viral infection, transmission and pathogenesis; predict potential host and how viral escape from immune system; prevent coronavirus infection or develop treatment therapy. Herein, [...] Read more.
Cellular receptor recognition exerts fundamental roles during coronavirus infection. Clarifying the regulatory mechanism of virus receptor helps to better understand viral infection, transmission and pathogenesis; predict potential host and how viral escape from immune system; prevent coronavirus infection or develop treatment therapy. Herein, we summarize current understanding of host receptor recognition mechanisms in the different genera of coronavirus family. And we also review diverse methodologies of identification and clarification of virus receptors. The integration of structural biology, multi-omics, computational predictions, synthetic biology and artificially engineered viral receptors, provide a powerful framework for elucidating coronavirus–receptor interactions. This also supports the development of broad-spectrum antiviral agents, smart biosensors, and intervention strategies against emerging coronaviruses. Full article
(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))
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9 pages, 3088 KB  
Communication
Hollow Protein Fibers Templated Synthesis of Pt/Pd Nanostructures with Peroxidase-like Activity
by Beizhe Huang, Mengting Fan, Yuhan Li, Ting Zhang and Jianting Zhang
Viruses 2025, 17(12), 1627; https://doi.org/10.3390/v17121627 - 16 Dec 2025
Viewed by 298
Abstract
Supramolecular proteins have emerged as promising templates for guiding metal ion mineralization into well-defined nanomaterials because of their structural versatility and chemical diversity. However, the precise control of metal ion nucleation on the different reactive sites of protein templates remains challenging. In this [...] Read more.
Supramolecular proteins have emerged as promising templates for guiding metal ion mineralization into well-defined nanomaterials because of their structural versatility and chemical diversity. However, the precise control of metal ion nucleation on the different reactive sites of protein templates remains challenging. In this study, a genetically engineered hollow tobacco mosaic virus protein fiber (TMVF) with excellent structural stability was employed to achieve selective mineralization of noble metal nanostructures either on its external surface or within its internal channel. Moreover, the Pt/Pd bimetallic nanowire (NW) was also successfully prepared by co-depositing Pt and Pd on the TMVF. The bimetallic NWs demonstrated a peroxidase-like activity, which enabled their application for cholesterol detection by cooperating with cholesterol oxidase. Full article
(This article belongs to the Special Issue Application of Genetically Engineered Plant Viruses)
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13 pages, 1608 KB  
Article
Characteristics and Influencing Factors Among Newly Diagnosed HIV-1 Patients with Non-Marital, Non-Commercial Heterosexual Contact in Lishui, China (2020–2024)
by Jianhua Mei, Jinkai Li, Xiaolei Chen, Liyang Qiu, Haifang Zhang, Jie Yu, Ling Ye, Deyong Zhang, Dongqing Cheng and Xiuying Chen
Viruses 2025, 17(12), 1626; https://doi.org/10.3390/v17121626 - 16 Dec 2025
Viewed by 370
Abstract
The increasing proportion of HIV-1 infections transmitted via non-marital non-commercial heterosexual contact (NMNCHC) in China necessitates a deeper understanding of its local characteristics. This study investigated the epidemiological, molecular network, and drug-resistant profiles among 400 newly diagnosed HIV-1 patients infected via non-marital heterosexual [...] Read more.
The increasing proportion of HIV-1 infections transmitted via non-marital non-commercial heterosexual contact (NMNCHC) in China necessitates a deeper understanding of its local characteristics. This study investigated the epidemiological, molecular network, and drug-resistant profiles among 400 newly diagnosed HIV-1 patients infected via non-marital heterosexual contact (NMHC), specifically its non-commercial subtype, in Lishui from 2020–2024. HIV-1 pol gene sequences were analyzed for subtypes, drug resistance mutations, and transmission clusters using phylogenetic and network methods (genetic distance threshold: 0.9%). The overall prevalence of transmitted drug resistance (TDR) was 13.3%, an intermediate level exceeding the national average, driven predominantly by NNRTI resistance (6.3%). High-level resistance to NVP (3.0%) and EFV (2.75%) was observed. CRF08_BC (43.8%) was the dominant subtype. Multivariate analysis identified female gender and higher education as significant risk factors for NMNCHC acquisition. Molecular network analysis incorporated 55.3% of cases, revealing clusters predominantly composed of middle-aged and elderly males, with CRF08_BC and CRF01_AE showing higher NMNCHC transmission risk within networks. These findings underscore an evolving epidemic with significant TDR and highlight the urgent need for targeted interventions, including enhanced resistance surveillance and focused strategies for the concealed NMNCHC population, to curb local HIV-1 transmission. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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17 pages, 3263 KB  
Article
TSWV Infection Differentially Reshapes the Symbiotic Microbiome of Two Frankliniella Thrips Species
by Eeshita Mandal, Nuttapol Noirungsee, Terd Disayathanoowat and Eui-Joon Kil
Viruses 2025, 17(12), 1625; https://doi.org/10.3390/v17121625 - 16 Dec 2025
Viewed by 291
Abstract
Vectoring tomato spotted wilt virus (TSWV) by two well-known thrips species, Frankliniella occidentalis Pergande and F. intonsa Trybom (Thysanoptera: Thripidae), is facilitated in different ways. Symbiotic bacteria positively influence thrips fitness, but the interaction between these bacteria and tospovirus inside the thrips’ body [...] Read more.
Vectoring tomato spotted wilt virus (TSWV) by two well-known thrips species, Frankliniella occidentalis Pergande and F. intonsa Trybom (Thysanoptera: Thripidae), is facilitated in different ways. Symbiotic bacteria positively influence thrips fitness, but the interaction between these bacteria and tospovirus inside the thrips’ body remains unknown. Metagenomic profiling of symbionts in nonviruliferous and viruliferous Frankliniella thrips was performed to elucidate the interactions between symbiotic bacteria and the virus. A total of 97 operational taxonomic units (OTUs) were identified by profiling the microbes, where Proteobacteria was the most abundant phylum, with a high richness in Serratia spp. F. occidentalis showed lower variation in bacterial diversity between nonviruliferous and viruliferous treatments than F. intonsa. RT-qPCR validation for Serratia and Escherichia revealed opposite abundance patterns between the two thrips species. In contrast, Enterobacteriaceae and Pantoea showed similar patterns with higher abundance in nonviruliferous conditions. Wolbachia was detected exclusively in F. intonsa, with a higher bacterial titer in the viruliferous sample. Our findings suggest that TSWV association may influence the abundance of different bacterial symbionts within the thrips’ body, potentially via induction of antimicrobial peptides in response to viral invasion, and to our knowledge this is the first report addressing this tripartite interaction. These findings improve our understanding of how virus–symbiont association contributes to thrips vector competence. Full article
(This article belongs to the Special Issue Molecular Virus–Insect Interactions, 2nd Edition)
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20 pages, 721 KB  
Review
Does Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Represent a Poly-Herpesvirus Post-Virus Infectious Disease?
by Maria Eugenia Ariza, Irene Mena Palomo and Marshall V. Williams
Viruses 2025, 17(12), 1624; https://doi.org/10.3390/v17121624 - 16 Dec 2025
Viewed by 1094
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute “flu-like” symptoms, suggesting a role [...] Read more.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute “flu-like” symptoms, suggesting a role for viruses. However, no single virus has been identified as the only etiological agent. This may reflect the approach employed or more strongly the central dogma associated with herpesviruses replication, which states that a herpesvirus exists in two states, either lytic or latent. The purpose of this review is to address the role that abortive lytic replication may have in the pathogenesis of ME/CFS and other post-acute viral infections and also to raise awareness that these syndromes might be poly-herpesviruses mediated diseases. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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14 pages, 1588 KB  
Article
Study of the Activity of the Staphylococcus aureus Phage vB_SaS_GE1 Against MRSA Clinical Isolates and Its Impact on the Formation of Dual-Species Biofilms with P. aeruginosa
by Nino Grdzelishvili, Davit Lazviashvili, Aleksandra Kurowska, Krzysztof Jakub Pawlik, Łukasz Łaczmanski, Elene Kakabadze, Elene Zhuravliova, Nina Chanishvili and Nata Bakuradze
Viruses 2025, 17(12), 1623; https://doi.org/10.3390/v17121623 - 16 Dec 2025
Viewed by 449
Abstract
Bacteriophage therapy is regarded as a promising alternative for treating and preventing antibiotic-resistant bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent and difficult-to-treat pathogens. S. aureus also contributes to the formation of both single- and mixed-species biofilms. Treating biofilms [...] Read more.
Bacteriophage therapy is regarded as a promising alternative for treating and preventing antibiotic-resistant bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent and difficult-to-treat pathogens. S. aureus also contributes to the formation of both single- and mixed-species biofilms. Treating biofilms remains a major challenge for antibiotic-based eradication of pathogens, as the biofilm matrix provides a protective barrier for bacteria. The selection of highly active phages targeting S. aureus is therefore crucial for medical applications, given the high prevalence and drug resistance of this pathogen. In this study, S. aureus phage vB_SaS_GE1 (GE1) was isolated and characterized as a potential therapeutic agent. The phage was isolated and propagated, and its host range was determined using standard methods. Whole-genome sequencing and annotation of the phage DNA were performed. A time–kill assay and evaluation of the anti-biofilm activity of the Staphylococcus phage, both alone and in combination with Pseudomonas phage GEC_PNG3 (PNG3) on mixed-species biofilms, were conducted. The results indicated that GE1 is a lytic phage that does not carry virulence-determining genes. The time–kill assay demonstrated sustained lytic activity of GE1 without the emergence of phage-resistant mutants in the tested MRSA strains. Although phage treatment increased biofilm matrix production compared to the control, the viable cell count within the biofilms was reduced. Overall, the characteristics assessed indicate that vB_SaS_GE1 is safe and exhibits strong antibacterial activity against MRSA strains. Full article
(This article belongs to the Collection Phage Therapy)
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11 pages, 495 KB  
Article
Sociodemographic Associations and COVID-19 Symptoms Following One Year of Molecular Screening for SARS-CoV-2 Among Healthcare Workers
by Viviane Campos Barbosa de Sena, Michelle Oliveira, Rejane Alencar Saldanha, Larissa Vicenza, Tais Hanae Kasai Brunswick, Bernardo Tura, Helena Cramer Veiga Rey, Adriana Bastos Carvalho, Antônio Carlos Campos de Carvalho, Djane Braz Duarte, Dayde Lane Mendonça da Silva and Daniel Arthur Barata Kasal
Viruses 2025, 17(12), 1622; https://doi.org/10.3390/v17121622 - 16 Dec 2025
Viewed by 268
Abstract
Background: During the COVID-19 pandemic, high rates of infection with SARS-CoV-2 were reported in healthcare workers (HCWs), among whom asymptomatic individuals had high potential to spread the virus while assisting high-risk patients. This study conducted routine SARS-CoV-2 screening among the staff of a [...] Read more.
Background: During the COVID-19 pandemic, high rates of infection with SARS-CoV-2 were reported in healthcare workers (HCWs), among whom asymptomatic individuals had high potential to spread the virus while assisting high-risk patients. This study conducted routine SARS-CoV-2 screening among the staff of a specialized cardiology hospital in Brazil during 2022 and 2023, while also evaluating variables associated with infection and the occurrence of symptoms. Methods: A prospective cohort study of 94 HCWs with biweekly RT-PCR screening was performed, employing RT-PCR from nasal swabs. Results: Participants aged 50.9 ± 10.2 years and were predominantly female (85.1%) and non-white (56.4%). The follow-up period was 576.4 ± 185.9 days, and most participants worked in the intensive care unit/emergency department (34%). Although the HCWs with the highest COVID-19 rates before inclusion were technicians/graduates (67.3%) and non-white individuals (57.7%), these groups presented lower infection rates at follow-up (p < 0.001, CI 95% 2.924–27.93; and p = 0.02, CI 95% 0.129–0.859, respectively). The number of asymptomatic cases increased during the study (p = 0.001), and simultaneous infection upsurges occurred in different hospital departments. Interpretation: These data highlight the association between educational level and the risk of SARS-CoV-2 infection in HCWs. The synchronicity of cases in different hospital departments offers insights about the nosocomial spread of SARS-CoV-2. The increase in the number of asymptomatic infections with repeated infections suggests that regular molecular screening may contribute to increasing the safety of both patients and HCWs in a pandemic context. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 4th Edition)
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3 pages, 146 KB  
Editorial
Pestivirus 2024: Special Issue Editorial
by Benjamin J. Lamp and Christiane M. Riedel
Viruses 2025, 17(12), 1621; https://doi.org/10.3390/v17121621 - 16 Dec 2025
Viewed by 238
Abstract
Pestiviruses are well known in the veterinary field and include some of the most economically significant pathogens of ungulates, such as classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV) [...] Full article
(This article belongs to the Special Issue Pestivirus 2024)
13 pages, 1121 KB  
Brief Report
Co-Circulation of Tick-Borne Bandaviruses and Orthonairoviruses Across Humans, Livestock, and Rats in Pakistan: Serologic Evidence and Public Health Implications
by Muhammad Ammar, Shengyao Chen, Muhammad Saqib, Jingyuan Zhang, Awais-Ur-Rahman Sial, Asad Zia, Yaohui Fang, Muhammad Khalid Mansoor, Abulimiti Moming, Asim Shahzad, Rehman Hafeez, Aneela Javed, Ali Hassan, Ben Hu, Ali Zohaib, Shu Shen and Fei Deng
Viruses 2025, 17(12), 1620; https://doi.org/10.3390/v17121620 - 15 Dec 2025
Viewed by 354
Abstract
Tick-borne viruses (TBVs) pose significant public health and economic threats. Pakistan has endemic Crimean-Congo hemorrhagic fever virus (CCHFV), but evidence suggests broader TBV circulation. This study assessed the seroprevalence of thirteen TBVs (seven are members of the genus Orthonairovirus and six are members [...] Read more.
Tick-borne viruses (TBVs) pose significant public health and economic threats. Pakistan has endemic Crimean-Congo hemorrhagic fever virus (CCHFV), but evidence suggests broader TBV circulation. This study assessed the seroprevalence of thirteen TBVs (seven are members of the genus Orthonairovirus and six are members of the genus Bandavirus) in humans, livestock, and rats in Punjab, Pakistan. Serum samples (n = 794: 321 livestock, 253 human, and 220 rat) were collected from the Narowal, Lahore, and Faisalabad districts. Antibodies to viral NPs were detected using the luciferase immunoprecipitation system (LIPS). The overall seroprevalence was 19.14% (152/794); it was highest in livestock (27.10%), then humans (20.55%), and then rats (5.91%). The highest seroprevalence rates were 3.12% for CCHFV in livestock, 3.56% for Yezo virus (YEZV) in humans, and 0.91% for Tamdy virus (TAMV) and Tacheng tick virus 1 (TcTV-1) in rats. Neutralizing antibodies were detected against CCHFV (1 cattle, 4 humans), Bhanja virus (BHAV) (3 livestock, 1 rat), TAMV (1 cattle), Guertu virus (GTV) (1 cattle), and Dabie bandavirus (2 cattle). Sixteen samples showed antibodies to both orthonairoviruses and bandaviruses, indicating co-exposure. Further analysis showed that seropositivity was not randomly distributed. Livestock kept in commercial farming systems and people working mainly outdoors had distinctly higher exposure to TBVs than subsistence livestock and indoor workers. The results supported the circulation of TBVs among hosts within the close socio-economic/ecological integration area of Pakistan. These findings confirm the circulation of CCHFV, SFTSV, GTV, and TAMV; provide the first serologic evidence of BHAV in Pakistan; and underscore the need for further investigation into the potential circulation of additional TBVs. All results demonstrated that multiple TBVs have been circulating among humans, livestock, and rodents in Pakistan. Full article
(This article belongs to the Special Issue Tick-Borne Viruses 2026)
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20 pages, 3953 KB  
Article
Sequential Dengue Virus Infection in Marmosets: Histopathological and Immune Responses in the Liver
by Daniele Freitas Henriques, Livia M. N. Casseb, Milene S. Ferreira, Larissa S. Freitas, Hellen T. Fuzii, Carla Pagliari, Luciane Kanashiro, Paulo H. G. Castro, Gilmara A. Siva, Orlando Pereira Amador Neto, Valter M. Campos, Beatriz C. Belvis, Flavia B. dos Santos, Lilian R. M. de Sá and Pedro Fernando da Costa Vasconcelos
Viruses 2025, 17(12), 1619; https://doi.org/10.3390/v17121619 - 15 Dec 2025
Viewed by 269
Abstract
This study evaluated hepatic pathological and phenotypic alterations, along with the inflammatory response, following sequential dengue virus (DENV) infection in Callithrix penicillata, a relevant model for human endemic scenarios. Twenty-six animals were initially infected subcutaneously with DENV-3. Thirteen were euthanized between 1 and [...] Read more.
This study evaluated hepatic pathological and phenotypic alterations, along with the inflammatory response, following sequential dengue virus (DENV) infection in Callithrix penicillata, a relevant model for human endemic scenarios. Twenty-six animals were initially infected subcutaneously with DENV-3. Thirteen were euthanized between 1 and 7 days post-infection (dpi) to assess the acute phase, and up to 60 dpi for the convalescent phase. The remaining animals received a secondary DENV-2 infection two months later. Liver samples underwent histopathological and immunohistochemical analysis. Viral antigens were identified in hepatocytes, Kupffer cells, and Councilman bodies. Observed liver changes included apoptosis, lytic necrosis, midzonal inflammation, Kupffer cell hyperplasia and hypertrophy, sinusoidal dilation, and hemosiderin deposition. Both primary and secondary infections increased activated macrophages, NK cells, S-100 protein, and B lymphocytes. Primary infection was associated with elevated CD4+ T cells, IFN-γ, TGF-β, IL-10, and Fas expression, whereas secondary infection induced higher IFN-γ, TNF-α, IL-8, Fas, and VCAM levels. These findings mirror hepatic alterations in severe human dengue cases and underscore the role of direct viral effects and immune dysregulation in liver injury. The results support C. penicillata as a suitable non-human primate model for studying DENV pathogenesis. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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16 pages, 8221 KB  
Article
An Attenuated Recombinant Newcastle Disease Virus of Genotype VII Generated by Reverse Genetics
by Hongze Pang, Yidan Bo, Jiawei Chen, Yongzhi Xue, Baishi Lei, Kuan Zhao, Yu Huang, Wenming Jiang, Wuchao Zhang and Wanzhe Yuan
Viruses 2025, 17(12), 1618; https://doi.org/10.3390/v17121618 - 15 Dec 2025
Viewed by 376
Abstract
Genotype VII Newcastle disease virus (NDV) has been confirmed as the predominant epidemic strain in China. Traditional vaccine strains fail to provide complete immune protection when challenged with an epidemic strain. NDV vaccines with phylogenetic relationships closer to those of the endemic viruses [...] Read more.
Genotype VII Newcastle disease virus (NDV) has been confirmed as the predominant epidemic strain in China. Traditional vaccine strains fail to provide complete immune protection when challenged with an epidemic strain. NDV vaccines with phylogenetic relationships closer to those of the endemic viruses demonstrate improved protective efficacy in reducing viral shedding and transmission. This research seeks to develop attenuated vaccine strains that are specifically aligned with NDV genotype VII. A reverse genetics system for the genotype VII NDV HB strain was developed, successfully rescuing the attenuated recombinant virus aHB by substituting the fusion protein (F) cleavage site motif “112R-R-Q-K-R↓F117” with “112G-R-Q-G-R↓L117.” Recombinant aHB virus attenuation was verified by assessing the mean death time (MDT) and intracerebral pathogenicity index (ICPI). The attenuated aHB strain demonstrated greater proliferation titers than did the virulent HB and rHB strains both in vivo and in vitro. Furthermore, the genome exhibited significant genetic stability even after 10 passages in chicken embryos. When challenged with the HB strain of NDV genotype VII, the aHB-inactivated vaccine provided 100% protection to chickens and effectively prevented viral shedding. These findings indicate that recombinant aHB may serve as an effective vaccine candidate. Full article
(This article belongs to the Section Animal Viruses)
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14 pages, 7059 KB  
Article
Differences in the Phenotype of Bacterial and Viral Sepsis—A Prospective, Multicenter, Observational Study
by Fabian Perschinka, Georg Franz Lehner, Timo Mayerhöfer, Andrea Köhler, Walter Hasibeder, Christoph Krismer, Julia Killian, Dietmar Fries, Johannes Bösch, Norbert Perschinka, Peter Hohenauer, Nadine Perschinka, Anna Lisa Hackl and Michael Joannidis
Viruses 2025, 17(12), 1617; https://doi.org/10.3390/v17121617 - 14 Dec 2025
Viewed by 359
Abstract
Sepsis is defined as a dysregulated host response to an infection, leading to life-threatening organ dysfunction. While sepsis is most commonly the result of a bacterial infection, it may also be caused by viral pathogens. The aim of this study was to describe [...] Read more.
Sepsis is defined as a dysregulated host response to an infection, leading to life-threatening organ dysfunction. While sepsis is most commonly the result of a bacterial infection, it may also be caused by viral pathogens. The aim of this study was to describe differences in organ dysfunction patterns and inflammatory markers between bacterial and viral sepsis. In this prospective multicenter cohort study, adults meeting SEPSIS-3 criteria were recruited from four Austrian ICUs between 1 August 2021 and 1 April 2024, excluding those who were immunocompromised within the preceding 12 months. Ninety patients were enrolled, of whom 57 had bacterial and 33 viral sepsis. Inflammatory markers, including IL-6 and PCT, were higher at ICU admission in bacterial sepsis. Adjusted linear regression confirmed bacterial etiology as the only significant predictor of higher 48 h peak IL-6 and PCT values. Patients with viral sepsis typically fulfilled SEPSIS-3 criteria through respiratory and cardiovascular SOFA components, while other organ dysfunctions were less frequent. Significant differences in the phenotype of bacterial and viral sepsis were observed, characterized by distinct inflammatory profiles and differing patterns of organ dysfunction. These findings may support the improved differentiation of bacterial and viral etiologies in sepsis. Full article
(This article belongs to the Special Issue Cross-Pathogen Insights into Infectious Diseases: From Biomarkers to Burden and Therapeutic Strategies of Viral Pathogens)
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4 pages, 150 KB  
Editorial
Special Issue: “Innate Immunity to Virus Infection, 2nd Edition”
by Xinyu Zhang and Caijun Sun
Viruses 2025, 17(12), 1616; https://doi.org/10.3390/v17121616 - 14 Dec 2025
Viewed by 273
Abstract
The frequent emergence of highly pathogenic viruses globally has persistently threatened global health [...] Full article
(This article belongs to the Special Issue Innate Immunity to Virus Infection 2nd Edition)
23 pages, 1586 KB  
Review
CAR-T Cell Therapy for HIV Cure: Current Challenges, Advances and Future Directions
by Monica-Daniela Padurariu-Covit, Costinela Georgescu, Mihaela Andreescu, Iulia Chiscop, Catalin Plesea-Condratovici and Manuela Arbune
Viruses 2025, 17(12), 1615; https://doi.org/10.3390/v17121615 - 14 Dec 2025
Viewed by 1040
Abstract
Antiretroviral therapy (ART) effectively suppresses HIV replication but fails to eradicate latent reservoirs, leading to viral rebound after interruption. Chimeric antigen receptor (CAR) T-cell therapy offers a potential strategy to achieve durable remission. A systematic PubMed search (July 2020–June 2025) identified 253 studies [...] Read more.
Antiretroviral therapy (ART) effectively suppresses HIV replication but fails to eradicate latent reservoirs, leading to viral rebound after interruption. Chimeric antigen receptor (CAR) T-cell therapy offers a potential strategy to achieve durable remission. A systematic PubMed search (July 2020–June 2025) identified 253 studies on CAR-T therapy in HIV; 74 met inclusion criteria and were qualitatively analyzed. Preclinical data showed that CAR-T cells can recognize and eliminate infected cells, reach viral reservoirs, and persist long term, particularly when derived from hematopoietic stem cells. Dual-target and combination approaches with checkpoint inhibitors or latency-reversing agents enhanced antiviral efficacy. Early clinical studies confirmed safety and modest reservoir reduction. CAR-T cell therapy represents a promising step toward a functional HIV cure. Further optimization of design, integration with gene-editing technologies, and standardized clinical evaluation are required to confirm durable efficacy and safety. Full article
(This article belongs to the Special Issue HIV Reservoirs, Latency, and the Factors Responsible)
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17 pages, 8553 KB  
Article
Generating STEC-Specific Ackermannviridae Bacteriophages Through Tailspike Protein Chimerization
by Jose Gil, John Paulson, Henriett Zahn, Matthew Brown, Minh M. Nguyen and Stephen Erickson
Viruses 2025, 17(12), 1614; https://doi.org/10.3390/v17121614 - 14 Dec 2025
Viewed by 322
Abstract
Shiga toxin-producing Escherichia coli (STEC) pose a significant threat to public health and effective methods of detection are needed. The use of naturally occurring bacteriophages (phages) to detect E. coli has been well documented. However, detecting multiple serotypes at the same time often [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) pose a significant threat to public health and effective methods of detection are needed. The use of naturally occurring bacteriophages (phages) to detect E. coli has been well documented. However, detecting multiple serotypes at the same time often required multiple phages specific to individual serotypes. To limit the burden of complex cocktails, this study aimed to engineer phages with an expanded host range that allows each phage to contribute to detection across multiple STEC serogroups. Kutterviruses, in the Ackermannviridae family, contain four tailspike proteins (TSPs), each of which confers tropism to a different bacterial strain. The modular nature of TSPs allows for mixing receptor-binding domains from diverse phage types. The host range of the Kuttervirus CBA120 was modified by replacing its native tailspike proteins (TSPs) with chimeric versions incorporating receptor-binding domains from related and unrelated phages. A structure-guided approach was utilized to overcome minimal sequence similarity between donor and recipient phages and achieve novel functional TSP chimeras. Two engineered phage variants were created that collectively detect five STEC serogroups: O26, O45, O103, O111, and O157. Spotting and luciferase assays confirmed that the replacement TSPs were functional and the phages had acquired new host ranges. This study demonstrates the feasibility of engineering Ackermannviridae phages with customized host ranges for detecting multiple STEC strains. This approach has potential applications in developing improved phage-based bacterial detection, therapy, and biocontrol. Full article
(This article belongs to the Special Issue Biotechnological Applications of Phage and Phage-Derived Proteins 2025)
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