Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.09.008
YanYing Yan , Zhiqiang Wei , Min Zheng , Mengji Lu , Xueyu Wang
Hepatitis B virus (HBV) establishes chronic infection through strategic manipulation of host metabolic networks, driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma. Mechanistically, HBV reprograms core metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipid homeostasis, to fuel its replication machinery and evade immune surveillance. This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring, with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.
{"title":"HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis","authors":"YanYing Yan , Zhiqiang Wei , Min Zheng , Mengji Lu , Xueyu Wang","doi":"10.1016/j.virs.2025.09.008","DOIUrl":"10.1016/j.virs.2025.09.008","url":null,"abstract":"<div><div>Hepatitis B virus (HBV) establishes chronic infection through strategic manipulation of host metabolic networks, driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma. Mechanistically, HBV reprograms core metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipid homeostasis, to fuel its replication machinery and evade immune surveillance. This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring, with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 685-693"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193133","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.09.003
Lujia Sun , Bianying Feng , Zezhong Liu , Jingqi Chen , Xiangwen Hao , Shuai Xia , Lu Lu , Qiuhong Man , Shibo Jiang , Xinling Wang
{"title":"Antisera and antivirals targeting the conserved domains in SARS-CoV-2 S2 subunit are effective against ACE2-using MERSr-CoVs with spillover potential","authors":"Lujia Sun , Bianying Feng , Zezhong Liu , Jingqi Chen , Xiangwen Hao , Shuai Xia , Lu Lu , Qiuhong Man , Shibo Jiang , Xinling Wang","doi":"10.1016/j.virs.2025.09.003","DOIUrl":"10.1016/j.virs.2025.09.003","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 856-859"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081586","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.09.006
Yang Song , Weiwei Gai , Jiaxin Sun , Xiangyu Lv , Haojie Sang , Shuai Guo , Jingqiang Ren , Jingbo Zhai , Shubo Wen
{"title":"First identification of Tusavirus in calf intestinal tissue suggests interspecies transmission and genomic variation","authors":"Yang Song , Weiwei Gai , Jiaxin Sun , Xiangyu Lv , Haojie Sang , Shuai Guo , Jingqiang Ren , Jingbo Zhai , Shubo Wen","doi":"10.1016/j.virs.2025.09.006","DOIUrl":"10.1016/j.virs.2025.09.006","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 860-862"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186826","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}
Pub Date : 2025-10-01DOI: 10.1016/j.virs.2025.10.003
Jiantao Fu , Yifan Guo , Guoxiang Zheng , Zongxing Yang , Jinchuan Shi , Dingyan Yan , Jianhua Yu , Lijun Sun , Hongxin Zhao
In China, approximately 13% of people living with human immunodeficiency virus (HIV) (PLWH) are receiving lopinavir/ritonavir (LPV/r)-based regimens. These PLWH typically have a history of either treatment failure or intolerance to first-line efavirenz-based regimens. Given the considerable pill burden and adverse effects associated with LPV/r, treatment optimization is important for this population. This multicenter retrospective study aimed to evaluate the efficacy and safety of switching from LPV/r-based regimens to the single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Virological suppression rates (HIV-RNA < 40 copies/mL) were primarily compared between the 48-week periods before and after switching to BIC/FTC/TAF. CD4 counts and metabolic data were also assessed. A total of 461 PLWH were recruited between January 2021 and December 2023, with 92.2% being male, a median age of 38 years, and a median antiretroviral therapy duration of 8 years. Prior to initiating LPV/r, 23.0% (106/461) had documented virological failure. During LPV/r treatment, 18.9% (20/106) of these individuals experienced viral rebound. Among all participants, the overall virological suppression rates significantly increased from 94.6% (pre-switch) to 98.6% (post-switch) (P < 0.001). Notably, among participants with prior virological failure, suppression rates improved significantly from 81.1% to 97.2% (P < 0.001), whereas no significant difference was observed in those without such history (from 98.6% to 99.2%, P = 0.764). The median triglyceride level decreased from 2.4 mmol/L to 1.8 mmol/L (P < 0.001), while no difference in CD4 counts was observed. These findings demonstrate that BIC/FTC/TAF is an effective and metabolically favorable treatment option for PLWH switching from LPV/r based regimens, regardless of whether they have a prior history of virological failure.
{"title":"Efficacy and safety of switching from lopinavir/ritonavir-based regimens to bictegravir/emtricitabine/tenofovir alafenamide in people living with HIV: A multicenter retrospective study","authors":"Jiantao Fu , Yifan Guo , Guoxiang Zheng , Zongxing Yang , Jinchuan Shi , Dingyan Yan , Jianhua Yu , Lijun Sun , Hongxin Zhao","doi":"10.1016/j.virs.2025.10.003","DOIUrl":"10.1016/j.virs.2025.10.003","url":null,"abstract":"<div><div>In China, approximately 13% of people living with human immunodeficiency virus (HIV) (PLWH) are receiving lopinavir/ritonavir (LPV/r)-based regimens. These PLWH typically have a history of either treatment failure or intolerance to first-line efavirenz-based regimens. Given the considerable pill burden and adverse effects associated with LPV/r, treatment optimization is important for this population. This multicenter retrospective study aimed to evaluate the efficacy and safety of switching from LPV/r-based regimens to the single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Virological suppression rates (HIV-RNA < 40 copies/mL) were primarily compared between the 48-week periods before and after switching to BIC/FTC/TAF. CD4 counts and metabolic data were also assessed. A total of 461 PLWH were recruited between January 2021 and December 2023, with 92.2% being male, a median age of 38 years, and a median antiretroviral therapy duration of 8 years. Prior to initiating LPV/r, 23.0% (106/461) had documented virological failure. During LPV/r treatment, 18.9% (20/106) of these individuals experienced viral rebound. Among all participants, the overall virological suppression rates significantly increased from 94.6% (pre-switch) to 98.6% (post-switch) (<em>P</em> < 0.001). Notably, among participants with prior virological failure, suppression rates improved significantly from 81.1% to 97.2% (<em>P</em> < 0.001), whereas no significant difference was observed in those without such history (from 98.6% to 99.2%, <em>P</em> = 0.764). The median triglyceride level decreased from 2.4 mmol/L to 1.8 mmol/L (<em>P</em> < 0.001), while no difference in CD4 counts was observed. These findings demonstrate that BIC/FTC/TAF is an effective and metabolically favorable treatment option for PLWH switching from LPV/r based regimens, regardless of whether they have a prior history of virological failure.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 835-841"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337464","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}
Pub Date : 2025-08-01DOI: 10.1016/j.virs.2025.07.002
Yecheng Zhang , Xinlei Ji , Dan Huang , Gen Lu , Xinwen Chen
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
{"title":"The coronavirus 3CL protease: Unveiling its complex host interactions and central role in viral pathogenesis","authors":"Yecheng Zhang , Xinlei Ji , Dan Huang , Gen Lu , Xinwen Chen","doi":"10.1016/j.virs.2025.07.002","DOIUrl":"10.1016/j.virs.2025.07.002","url":null,"abstract":"<div><div>The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 4","pages":"Pages 509-519"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601671","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}
Pub Date : 2025-08-01DOI: 10.1016/j.virs.2025.07.003
Lu Yang , Linhua Wang , Qian Liu , Xu Zhang , Yuexin Luo , Junbiao Xue , Xinpu Yang , Maria G. Byazrova , Alexander V. Filatov , Sheng-Ce Tao , Wei Xiao , Chaohong Liu
SARS-CoV-2 infection and vaccination both trigger immune responses. The former leads to naturally acquired immunity, while the latter induces active immunity through artificial means. However, the distinct immune effects of vaccination and infection, as well as their underlying mechanisms, require further clarification. In this study, we compared the peripheral B cell differentiation, serological differences and the expression level of BCR signaling molecules between the vaccinated and recovered group. The vaccinated group exhibited reduced RBD-specific B cell differentiation and lower CD86 signal intensity on memory B cells, but enhanced BCR signaling in B cells. Regarding metabolic signaling, the vaccinated group had elevated expression levels of pS6, c-Myc, pmTOR, and pSTAT5, suggesting that the STAT5-c-Myc axis plays a role in regulating B cell metabolism. Additionally, proteome microarray analysis revealed that the serum of the vaccinated group contained higher levels of IgG antibodies against the SARS-CoV-2 N-Nter protein and IgA antibodies specific to the SARS-CoV-2 S1 protein. In summary, these findings indicate that the vaccinated group develops a more robust coronavirus-specific immune response, with enhanced BCR signaling and metabolic activity compared to the recovered group. These insights might contribute to the optimization of SARS-CoV-2 vaccine design.
{"title":"STAT5-c-Myc-axis regulates B cell metabolism in vaccinated individuals and COVID-19 recovered patients","authors":"Lu Yang , Linhua Wang , Qian Liu , Xu Zhang , Yuexin Luo , Junbiao Xue , Xinpu Yang , Maria G. Byazrova , Alexander V. Filatov , Sheng-Ce Tao , Wei Xiao , Chaohong Liu","doi":"10.1016/j.virs.2025.07.003","DOIUrl":"10.1016/j.virs.2025.07.003","url":null,"abstract":"<div><div>SARS-CoV-2 infection and vaccination both trigger immune responses. The former leads to naturally acquired immunity, while the latter induces active immunity through artificial means. However, the distinct immune effects of vaccination and infection, as well as their underlying mechanisms, require further clarification. In this study, we compared the peripheral B cell differentiation, serological differences and the expression level of BCR signaling molecules between the vaccinated and recovered group. The vaccinated group exhibited reduced RBD-specific B cell differentiation and lower CD86 signal intensity on memory B cells, but enhanced BCR signaling in B cells. Regarding metabolic signaling, the vaccinated group had elevated expression levels of pS6, c-Myc, pmTOR, and pSTAT5, suggesting that the STAT5-c-Myc axis plays a role in regulating B cell metabolism. Additionally, proteome microarray analysis revealed that the serum of the vaccinated group contained higher levels of IgG antibodies against the SARS-CoV-2 N-Nter protein and IgA antibodies specific to the SARS-CoV-2 S1 protein. In summary, these findings indicate that the vaccinated group develops a more robust coronavirus-specific immune response, with enhanced BCR signaling and metabolic activity compared to the recovered group. These insights might contribute to the optimization of SARS-CoV-2 vaccine design.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 4","pages":"Pages 571-578"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601730","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}
Pub Date : 2025-08-01DOI: 10.1016/j.virs.2025.06.004
Yiwei Shi , Letian Fang , Cixiu Li , Peng Li , Jiluo Liu , Yifan Chen , Yue Zhao , Zishuai Li , Shuqi Liu , Yibo Ding , Xinyu Zhou , Dongming Jiang , Jiaying Shen , Zihan Zhang , Junheng Lyu , Rui Pu , Xiaojie Tan , Jianhua Yin , Weifeng Shi , Guangwen Cao
Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions. We conducted meta-transcriptomic sequencing of 226 mammals (bats, rodents, hedgehogs, and shrews) representing 20 species collected across eight cities in south China between 2018 and 2024. Samples included internal organs, oropharyngeal and anal swabs, and feces. We identified 63 vertebrate-associated viruses, including 34 novel viruses. Phylogenetic analysis revealed six viruses with potential infection risks to humans or domestic animals due to their close phylogenetic relationships with known pathogens. Cross-species transmission was observed in 14.3% (9/63) of viruses, shared by at least two host species, with bats, particularly Rhinolophus and Hipposideros, serving as key hubs for viral circulation and zoonotic spillover. Virome composition varied substantially among mammalian species and geographic regions (adonis test, R2 = 0.50, P = 0.001). Generalized linear models quantified the roles of host taxonomy, ecotypes, and meteorological factors in shaping viral diversity, demonstrating host taxonomy (at the order level) as a predominant role (25.70% deviance explained), followed by ecotypes (10.27% deviance explained). Phylogenetic analysis conducted using our betacoronavirus sequences, as well as betacoronavirus sequences derived from 2.0 × 104 bats sampled in China between July 2013 and March 2024, revealed that no betacoronaviruses exhibited closer phylogenetic relationships to SARS-CoV-2 than the known strains (e.g., RaTG13). These findings provide critical insights into virus evolution, transmission, and ecological determinants, which are essential for the prevention of emerging infectious diseases.
哺乳动物是人类传染病的重要宿主，病毒的外溢与气候条件有关。研究人员对2018年至2024年间在中国南方8个城市收集的226种哺乳动物（蝙蝠、啮齿动物、刺猬和鼩鼱）进行了meta转录组测序。样本包括内脏、口咽和肛门拭子以及粪便。我们鉴定出63种脊椎动物相关病毒，包括34种新型病毒。系统发育分析发现6种病毒与已知病原体有密切的系统发育关系，对人类或家畜具有潜在的感染风险。在14.3%（9/63）的病毒中观察到跨物种传播，至少由两个宿主物种共享，其中蝙蝠，特别是犀牛和希波sideros，是病毒传播和人畜共患溢出的关键枢纽。病毒组组成在哺乳动物种类和地理区域之间存在显著差异（adonis R2 = 0.50, P = 0.001）。广义线性模型量化了宿主分类学、生态型和气象因素在塑造病毒多样性中的作用，表明宿主分类学（在目级）是主要作用（25.70%的偏差解释），其次是生态型（10.27%的偏差解释）。利用我们的冠状病毒序列以及2013年7月至2024年3月在中国采样的2.0 × 104只蝙蝠的冠状病毒序列进行的系统发育分析显示，没有一种冠状病毒与SARS-CoV-2的系统发育关系比已知毒株（例如RaTG13）更密切。这些发现为病毒进化、传播和生态决定因素提供了重要见解，这对预防新发传染病至关重要。
{"title":"Virome diversity in small mammals from south China: Insights into virus evolution, transmission, and ecology","authors":"Yiwei Shi , Letian Fang , Cixiu Li , Peng Li , Jiluo Liu , Yifan Chen , Yue Zhao , Zishuai Li , Shuqi Liu , Yibo Ding , Xinyu Zhou , Dongming Jiang , Jiaying Shen , Zihan Zhang , Junheng Lyu , Rui Pu , Xiaojie Tan , Jianhua Yin , Weifeng Shi , Guangwen Cao","doi":"10.1016/j.virs.2025.06.004","DOIUrl":"10.1016/j.virs.2025.06.004","url":null,"abstract":"<div><div>Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions. We conducted <em>meta</em>-transcriptomic sequencing of 226 mammals (bats, rodents, hedgehogs, and shrews) representing 20 species collected across eight cities in south China between 2018 and 2024. Samples included internal organs, oropharyngeal and anal swabs, and feces. We identified 63 vertebrate-associated viruses, including 34 novel viruses. Phylogenetic analysis revealed six viruses with potential infection risks to humans or domestic animals due to their close phylogenetic relationships with known pathogens. Cross-species transmission was observed in 14.3% (9/63) of viruses, shared by at least two host species, with bats, particularly <em>Rhinolophus</em> and <em>Hipposideros</em>, serving as key hubs for viral circulation and zoonotic spillover. Virome composition varied substantially among mammalian species and geographic regions (adonis test, <em>R</em><sup><em>2</em></sup> = 0.50, <em>P</em> = 0.001). Generalized linear models quantified the roles of host taxonomy, ecotypes, and meteorological factors in shaping viral diversity, demonstrating host taxonomy (at the order level) as a predominant role (25.70% deviance explained), followed by ecotypes (10.27% deviance explained). Phylogenetic analysis conducted using our betacoronavirus sequences, as well as betacoronavirus sequences derived from 2.0 × 10<sup>4</sup> bats sampled in China between July 2013 and March 2024, revealed that no betacoronaviruses exhibited closer phylogenetic relationships to SARS-CoV-2 than the known strains (e.g., RaTG13). These findings provide critical insights into virus evolution, transmission, and ecological determinants, which are essential for the prevention of emerging infectious diseases.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 4","pages":"Pages 520-534"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529821","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}
Pub Date : 2025-08-01DOI: 10.1016/j.virs.2025.07.001
Shuting Huo , Changcheng Wu , Zhenyong Qi , Jiewei Sun , Xin Meng , Jingdong Song , Zhongxian Zhang , Liye Jin , Chang Shu , Zhifeng Lin , Weibang Huo , Yao Deng , Li Zhao , Jiandong Li , Wenjie Tan
Ectromelia virus (ECTV), a member of the Orthopoxvirus genus, serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses. Although genomic data on ECTV remains limited, we report the isolation and characterization of a novel strain, ECTV-C-Tan-GD01, obtained from rodents in Guangdong Province, China. Nanopore sequencing yielded a complete genome (199 annotated genes, including one gene truncated at the C-terminus) with inverted terminal repeats (ITRs) harboring a conserved hairpin structure. Notably, a frameshift-inducing “G” deletion in the EV159 gene resulted in the truncation of a semaphorin-like protein. In vitro assays demonstrated cell-associated viral replication kinetics, with maximum titers achieved earlier in Vero/HeLa cells (72 h) than in BHK-21/CEF cells (84 h). Murine challenge experiments revealed extreme virulence (LD50 < 1 plaque-forming unit (PFU) via intranasal/footpad routes) and hepatosplenic tropism. Furthermore, ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures: a single dose of vaccinia virus Tiantan (VTT) or non-replicating vaccinia virus Tiantan (NTV) conferred cross-protection, while tecovirimat (ST-246), cidofovir (CDV), and brincidofovir (initially CMX001) significantly reduced viral loads and pathology. This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.
电疣病毒（ECTV）是正痘病毒属的一员，既是小鼠痘的病原体，也是研究高致病性正痘病毒的关键替代模型。虽然关于ECTV的基因组数据仍然有限，但我们报道了从中国广东省啮齿动物中分离和鉴定的一种新菌株ECTV- c - tan - gd01。纳米孔测序得到了一个完整的基因组（199个注释基因，包括一个在c端被截断的基因），其反向末端重复序列（ITRs）包含一个保守的发夹结构。值得注意的是，EV159基因中引起帧移的“G”缺失导致信号蛋白样蛋白的截断。体外实验证实了细胞相关的病毒复制动力学，Vero/HeLa细胞（72小时）比BHK-21/CEF细胞（84小时）更早达到最大滴度。小鼠攻毒实验显示出极强的毒力（LD50 < 1斑块形成单位（PFU），经鼻内/足垫途径）和肝脾性。此外，ECTV-C-Tan-GD01在评估正痘病毒应对措施方面显示出效用：单剂量天坛牛痘病毒（VTT）或非复制性天坛牛痘病毒（NTV）具有交叉保护作用，而tecovirimat （ST-246）、西多福韦（CDV）和brincidofovir（最初为CMX001）可显著降低病毒载量和病理。本研究建立了ECTV-C-Tan-GD01作为探测正痘病毒进化和促进治疗开发的双重资源。
{"title":"Identification of a novel ectromelia virus from rodent: Implications for use as an in vivo infection model for vaccine and antiviral research","authors":"Shuting Huo , Changcheng Wu , Zhenyong Qi , Jiewei Sun , Xin Meng , Jingdong Song , Zhongxian Zhang , Liye Jin , Chang Shu , Zhifeng Lin , Weibang Huo , Yao Deng , Li Zhao , Jiandong Li , Wenjie Tan","doi":"10.1016/j.virs.2025.07.001","DOIUrl":"10.1016/j.virs.2025.07.001","url":null,"abstract":"<div><div>Ectromelia virus (ECTV), a member of the <em>Orthopoxvirus</em> genus, serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses. Although genomic data on ECTV remains limited, we report the isolation and characterization of a novel strain, ECTV-C-Tan-GD01, obtained from rodents in Guangdong Province, China. Nanopore sequencing yielded a complete genome (199 annotated genes, including one gene truncated at the C-terminus) with inverted terminal repeats (ITRs) harboring a conserved hairpin structure. Notably, a frameshift-inducing “G” deletion in the <em>EV159</em> gene resulted in the truncation of a semaphorin-like protein. <em>In vitro</em> assays demonstrated cell-associated viral replication kinetics, with maximum titers achieved earlier in Vero/HeLa cells (72 h) than in BHK-21/CEF cells (84 h). Murine challenge experiments revealed extreme virulence (LD<sub>50</sub> < 1 plaque-forming unit (PFU) via intranasal/footpad routes) and hepatosplenic tropism. Furthermore, ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures: a single dose of vaccinia virus Tiantan (VTT) or non-replicating vaccinia virus Tiantan (NTV) conferred cross-protection, while tecovirimat (ST-246), cidofovir (CDV), and brincidofovir (initially CMX001) significantly reduced viral loads and pathology. This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 4","pages":"Pages 601-612"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601729","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}
Pub Date : 2025-08-01DOI: 10.1016/j.virs.2025.06.007
Yang Yang , Qiuyue Wu , Xueyan Liu , Hongjian Zhou , Jianzhen Lei , Lan Luo , Xinyi Xia
microRNAs (miRNAs) derived from viruses, have been detected in body fluids and are known to regulate the expression of host genes. Recent evidence indicates that SARS-CoV-2-encoded miRNAs could contribute to pulmonary disease. Pulmonary fibrosis is an important complication in SARS-CoV-2 infected patients, either during hospitalization or after discharge, however, the underlying mechanisms are not fully elucidated. Here, we report a SARS-CoV-2-encoded miRNA, miR-nsp3-3p, facilitates host pulmonary fibrosis by inhibiting expression of activated leukocyte cell adhesion molecule (ALCAM) and promoting epithelial-mesenchymal transition (EMT). First, we detected miR-nsp3-3p in clinical specimens and found it was remarkably increased in throat swabs and alveolar lavage fluids from severe/critical COVID-19 patients compared to control groups or mild/moderate patients. We further revealed that adeno-associated virus (AAV)-nsp3 infection can induce pulmonary fibrosis in BALB/c mice while miR-nsp3-3p antagomirs can reverse that, and ALCAM was found to be as a target gene of miR-nsp3-3p. miR-nsp3-3p overexpression can inhibit the expression of ALCAM and promote EMT of pulmonary epithelial cells. Moreover, overexpression of ALCAM can reverse the miR-nsp3-3p-induced EMT and fibrosis. These findings highlight the essential role of SARS-CoV-2-encoded miRNAs in promoting the pathological progression of lung disease, and provide novel insights into the interactions between viral miRNAs and host pathology.
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