VirologyPub Date : 2025-03-17DOI: 10.1016/j.virol.2025.110504
Manman Qiu , Rongrong Wei , Qicheng Zhang , Jiawei Zhao , Hongkai Zhang , Juan Tan , Wentao Qiao
{"title":"ISG15 depletion enhances oHSV-1 replication and antitumor efficacy in oral squamous cell carcinoma","authors":"Manman Qiu , Rongrong Wei , Qicheng Zhang , Jiawei Zhao , Hongkai Zhang , Juan Tan , Wentao Qiao","doi":"10.1016/j.virol.2025.110504","DOIUrl":"10.1016/j.virol.2025.110504","url":null,"abstract":"<div><div>Oncolytic viruses (OVs) represent a promising experimental therapy for a range of cancers, including oral squamous cell carcinoma (OSCC). In this study, oHSV refers to an oncolytic virus engineered from HSV-1(Herpes Simplex Virus Type 1). The oHSV-1 is an oncolytic virus derived from HSV-1, where both copies of the ICP34.5 coding sequences have been replaced with the EGFP gene, and the ICP47 gene has been deleted. In previous studies, resistance was observed in certain SCC15 xenograft models treated with oncolytic herpes simplex viruses (oHSV-1). Primary tumor cells were extracted from these resistant models, followed by RNA sequencing with SCC15 cells as controls. Analysis revealed that ISG15 expression was upregulated in the resistant primary cells, as well as in HSV-infected breast cancer cells (GSE137757). In this study, we confirmed that knockdown ISG15 in SCC15 cells enhanced oHSV-1 replication, while ISG15 overexpression suppressed it. Mechanistic studies demonstrated that ISG15 inhibits oHSV-1 replication via ISGylation. To improve the therapeutic efficacy of oHSV-1, an oHSV-1 variant expressing ISG15-targeting short hairpin RNA (shRNA), termed oHSV-1-shISG15, was engineered. oHSV-1-shISG15 exhibited enhanced antitumor efficacy compared to oHSV-1 <em>in vitro</em> and i<em>n vivo</em>. These findings suggest that ISG15 depletion augments oHSV-1 replication in OSCC tumor cells through ISGylation inhibition. Meanwhile, this study provides a novel recombinant oncolytic virus to potentiate the efficacy of oncolytic herpes virotherapy.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110504"},"PeriodicalIF":2.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-13DOI: 10.1016/j.virol.2025.110501
Wanying Zou , Qingmei Li , Chunzhen Li , Zekun Meng , Yaning Sun , Suzhen Yang , Junqing Guo , Gaiping Zhang
{"title":"Fine mapping of conserved neutralizing epitopes within the VP2 protein of Senecavirus A using monoclonal antibodies","authors":"Wanying Zou , Qingmei Li , Chunzhen Li , Zekun Meng , Yaning Sun , Suzhen Yang , Junqing Guo , Gaiping Zhang","doi":"10.1016/j.virol.2025.110501","DOIUrl":"10.1016/j.virol.2025.110501","url":null,"abstract":"<div><div>Senecavirus A (SVA) is an emerging swine virus with global prevalence that causes vesicular disease (VD), clinically similar to foot-and-mouth disease (FMD), posing a significant concern for the swine industry. The capsid protein VP2 is a structural protein of SVA, playing a critical role in mediating viral entry into host cells and inducing the production of neutralizing antibodies. In this study, the SVA VP2 protein was expressed using the Bac-to-Bac baculovirus expression system. Six monoclonal antibodies (mAbs) targeting SVA VP2 protein were then produced by immunizing mice with the recombinant VP2 protein, named as 1A1F6, 3D5F9, 3E2C3, 5A6F5, 5F12D10 and 7H10C3, respectively. Among these, mAbs 1A1F6 and 7H10C3 exhibited neutralizing activity against SVA <em>in vitro</em> with IC<sub>50</sub> values of 0.64 μg/mL and 1.21 μg/mL, respectively. Finally, a linear B-cell neutralizing epitope of <sup>151</sup>SLQELN<sup>156</sup> on the SVA VP2 protein was identified by determining the reactivity of the neutralizing mAbs with the truncated VP2 protein followed by peptide scanning. Peptide mutation analysis showed that the residues Ser<sup>151</sup>, Leu<sup>152</sup>, Leu<sup>155</sup>, and Asn<sup>156</sup> within the epitope were essential for antibody binding. Multiple sequence alignment indicated that this epitope is highly conserved across various SVA strains. These findings provide a foundation for further studies on SVA and offer valuable support for the design of SVA vaccines.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110501"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-12DOI: 10.1016/j.virol.2025.110496
Wei Zhao , Jige Du , Jia Su , Jie Gao , Hongxu Bai , Daiyue Lv , Xiaochun Chen , Dongdong Liu , Guohua Wang , Qinghong Xue
{"title":"Comprehensive single-cell profiling of T and B cell subsets in mice reveals impacts on memory immune responses in FMDV infection","authors":"Wei Zhao , Jige Du , Jia Su , Jie Gao , Hongxu Bai , Daiyue Lv , Xiaochun Chen , Dongdong Liu , Guohua Wang , Qinghong Xue","doi":"10.1016/j.virol.2025.110496","DOIUrl":"10.1016/j.virol.2025.110496","url":null,"abstract":"<div><div>The impact of Foot-and-Mouth Disease Virus (FMDV) on memory immune responses has not been thoroughly investigated due to limited availability of immunological research tools. Using single-cell RNA sequencing, we identified specific gene markers for the majority of T and B cell subsets in the spleens of mice. Our findings indicate that FMDV infection significantly reduces the proportions of memory cell populations (e.g., memory B cells, memory CD4<sup>+</sup> T cells, and memory CD8<sup>+</sup> T cells) relative to their respective lymphocyte subsets (total B cells, CD4<sup>+</sup> T cells, and CD8<sup>+</sup> T cells) in the short term, impacting their functions. These alterations largely reverse over the long term. Specifically, FMDV infection primarily exerts its impacts on the function of memory cells by enhancing key immunological functions such as activation, proliferation, differentiation, and polarization, while simultaneously suppressing essential cellular biological functions including proliferation and metabolism. These impacts were significantly associated with <em>Fos</em>-related genes. Our study provides new insights into the immune evasion mechanisms of FMDV, establishes adult mice as potential models for FMDV immunological research, and offers valuable tools for single-cell RNA sequencing in murine immunological studies.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110496"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-12DOI: 10.1016/j.virol.2025.110499
Jayasri Das Sarma
{"title":"Murine β-coronavirus spike protein: A major determinant of neuropathogenic properties","authors":"Jayasri Das Sarma","doi":"10.1016/j.virol.2025.110499","DOIUrl":"10.1016/j.virol.2025.110499","url":null,"abstract":"<div><div>Coronaviruses have emerged as a significant challenge to human health. While earlier outbreaks of coronaviruses such as SARS-CoV and MERS-CoV posed serious threats, the recent SARS-CoV-2 pandemic has heightened interest in coronavirus research due to its pulmonary pathology, in addition to its neurological manifestations. In addition, the patients who have recovered from SARS-CoV-2 infection show long-term symptoms such as anosmia, brain fog and long COVID. A major hurdle in studying these viruses is the limited availability of specialized research facilities, emphasizing the need for prototype virus-based models to investigate the pathophysiology. The mouse hepatitis virus (MHV), a member of the β-coronavirus family, serves as an excellent model to unravel the mechanisms underlying virus-induced pathogenesis. This review highlights two decades of research efforts aimed at understanding the pathophysiological mechanism of coronavirus-induced diseases, focusing on the development of targeted recombinant strains to identify the minimal essential motif of the spike protein responsible for fusogenicity and neuropathogenicity. By synthesizing findings from these studies, the review identifies the most promising therapeutic targets against coronaviruses, paving the way for the development of pan-coronavirus antivirals.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110499"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-12DOI: 10.1016/j.virol.2025.110502
Jonathan P. Davies , Alejandra Ingunza , Bia Peña , Mayra Ochoa , Luis M. Franchi , Ana I. Gil , Kristen M. Ogden , Leigh M. Howard , Carlos G. Grijalva , Lars Plate , Claudio F. Lanata
{"title":"Proteomics as a complementary approach to measure norovirus infection in clinical samples","authors":"Jonathan P. Davies , Alejandra Ingunza , Bia Peña , Mayra Ochoa , Luis M. Franchi , Ana I. Gil , Kristen M. Ogden , Leigh M. Howard , Carlos G. Grijalva , Lars Plate , Claudio F. Lanata","doi":"10.1016/j.virol.2025.110502","DOIUrl":"10.1016/j.virol.2025.110502","url":null,"abstract":"<div><div>Norovirus (NoV) is a leading cause of global acute gastroenteritis, particularly in young children, with no current licensed vaccine. Epidemiological studies have shown that asymptomatic cases are common, and infected patients may test positive for prolonged periods; however, the impact of these phenomena on transmission and public health measures remains unclear. A major limiting factor is our ability to measure infection, which is constrained to real-time reverse transcription polymerase chain reaction or antibody-based assays, both of which are susceptible to loss of detection by rapid NoV evolution. This review highlights the potential for proteomics to overcome current technical limitations and advance basic science discovery and clinical research. Importantly, proteomics-based protein detection can span NoV, host, and microbiome proteins and could help identify host or microbiome factors that correlate with disease outcome. Further developing proteomics tools to complement existing diagnostic technologies will improve our ability to assess NoV pathogenesis and transmission, as well as therapeutic efficacy.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110502"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-10DOI: 10.1016/j.virol.2025.110478
Tobiasz Druciarek , Ioannis E. Tzanetakis
{"title":"Invisible vectors, visible impact: The role of eriophyoid mites in emaravirus disease dynamics","authors":"Tobiasz Druciarek , Ioannis E. Tzanetakis","doi":"10.1016/j.virol.2025.110478","DOIUrl":"10.1016/j.virol.2025.110478","url":null,"abstract":"<div><div>Emaraviruses are segmented, negative-sense RNA viruses that are transmitted by eriophyoid mites. Advances in virus detection and discovery have significantly improved our understanding of these viruses, yet several challenges persist. This review emphasizes the significant gaps in our knowledge of virus replication, transmission dynamics, and plant-virus-vector interactions and highlights the role of mite vectors in the epidemiology and control of emaraviruses. By bridging the knowledge gaps with advanced genomic tools such as high-throughput sequencing and bioinformatics and targeted acarological research we will achieve sustainable control strategies and reduce the impact of emaravirus-caused diseases.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110478"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-08DOI: 10.1016/j.virol.2025.110485
Qian Mao , Qin Luo , Sheng-Min Ma , Man Teng , Jun Luo
{"title":"Critical role of ferroptosis in viral infection and host responses","authors":"Qian Mao , Qin Luo , Sheng-Min Ma , Man Teng , Jun Luo","doi":"10.1016/j.virol.2025.110485","DOIUrl":"10.1016/j.virol.2025.110485","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent form of programmed cell death that plays a crucial role in regulating intracellular redox homeostasis and lipid metabolism, and in combating viral infections. Viruses have persistently evolved and adapted synergistically with their hosts over a long period and, to some extent, have been able to utilize ferroptosis to promote viral replication. Herein, we summarize the characteristics, mechanisms, and regulatory networks of ferroptosis and provide an overview of the key regulatory steps of ferroptosis involved in viral infection, together with the changes in host indicators and key regulatory signaling pathways. This study intends to deepen our understanding of the critical role of ferroptosis in viral infection, which will be meaningful for further revealing the mechanisms underlying the occurrence and progression of virus diseases, as well as for the future exploration of anti-viral strategies.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110485"},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-07DOI: 10.1016/j.virol.2025.110479
Marta Acchioni , Chiara Acchioni , John Hiscott , Marco Sgarbanti
{"title":"Corrigendum to “Origin and function of anti-interferon type I viral proteins” [Virology 605 (2025) 110456 1-12]","authors":"Marta Acchioni , Chiara Acchioni , John Hiscott , Marco Sgarbanti","doi":"10.1016/j.virol.2025.110479","DOIUrl":"10.1016/j.virol.2025.110479","url":null,"abstract":"","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110479"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-03-07DOI: 10.1016/j.virol.2025.110484
Junyu Tang , Leyi Wang , Weihuan Fang , Chia-Ming Su , Jineui Kim , Yijun Du , Dongwan Yoo
{"title":"Coinfection with bacterial pathogens and genetic modification of PRRSV-2 for suppression of NF-κB and attenuation of proinflammatory responses","authors":"Junyu Tang , Leyi Wang , Weihuan Fang , Chia-Ming Su , Jineui Kim , Yijun Du , Dongwan Yoo","doi":"10.1016/j.virol.2025.110484","DOIUrl":"10.1016/j.virol.2025.110484","url":null,"abstract":"<div><div>Porcine reproductive and respiratory syndrome virus (PRRSV) infects pulmonary alveolar macrophages and induces inflammation in the respiratory system. In swine farms, coinfection with PRRSV and bacterial pathogens is common and can result in clinically complicated outcomes, including porcine respiratory disease complex. Coinfection can cause excessive expressions of proinflammatory mediators and may lead to cytokine-storm-like syndrome. An immunological hallmark of PRRSV-2 is the bidirectional regulation of NF-κB with the nucleocapsid (N) protein identified as the NF-κB activator. We generated an NF-κB-silencing mutant PRRSV-2 by mutating the N gene to block its binding to PIAS1 [protein inhibitor of activated STAT-1 (signal transducer and activator of transcription 1)]. PIAS1 functions as an NF-κB repressor, and thus, the PIAS1-binding modified N-mutant PRRSV-2 became NF-κB activation-resistant in its phenotype. During coinfection of pigs with PRRSV-2 and <em>Streptococcus suis</em>, the N-mutant PRRSV-2 decreased the expression of proinflammatory cytokines and showed clinical attenuation. This review describes the coinfection of pigs with various pathogens, the generation of mutant PRRSV for NF-κB suppression, inflammatory profiles during bacterial coinfection, and the potential application of these findings to designing a new vaccine candidate for PRRSV-2.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"606 ","pages":"Article 110484"},"PeriodicalIF":2.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}