Virologica Sinica最新文献

英文中文

Ubiquitously expressed transcript isoform 2 (UXT-V2) restricts HSV-2 replication by targeting glycoprotein B for degradation through ubiquitin-proteasome pathway 泛素表达的转录异构体2 （UXT-V2）通过泛素-蛋白酶体途径靶向糖蛋白B降解，限制HSV-2的复制。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.08.004

Chuntian Li , Yuncheng Li , Ranqing Cheng , Miaomiao Li , Mudan Zhang , Zhiyuan Zhu , Ping Yang , Qinxue Hu , Yalan Liu

Herpes simplex virus 2 (HSV-2) is a major pathogen causing neonatal herpes and increasing the risk of human immunodeficiency virus 1 (HIV-1) infection. However, the mechanisms underlying host restriction of HSV-2 infection are still not fully understood. The ubiquitously expressed transcript isoform 2 (UXT-V2), an α-type prefoldin protein, functions as a versatile transcription factor associated with numerous human tumors, but its role in viral infection remains unclear. In this study, we found that ectopic expression of UXT-V2 significantly inhibited HSV-2 replication, while knockout of endogenously expressed UXT-V2 promoted HSV-2 proliferation. Further analysis revealed that UXT-V2 restricts HSV-2 replication independent of its role in regulating NF-κB. In the context of HSV-2 infection or in viral glycoprotein B (gB)-transfected cells, UXT-V2 facilitates K48-linked ubiquitination of gB, leading to its degradation via the proteasome pathway, thereby inhibiting viral replication. Furthermore, we identified that UXT-V2 interacts with gB, recruiting the E3 ligase TRIM21 to facilitate K48-linked ubiquitination of gB. HSV-2, in turn, reduces the abundance of UXT-V2 proteins both in vitro and in mice, highlighting the complexity of HSV-2-host interactions. Collectively, our findings, for the first time, demonstrate an anti-HSV-2 role of UXT-V2, unveiling a novel host immune defense mechanism involved in regulating glycoprotein homeostasis.

单纯疱疹病毒2 （HSV-2）是引起新生儿疱疹和增加人类免疫缺陷病毒1 （HIV-1）感染风险的主要病原体。然而，宿主限制2型单纯疱疹病毒感染的机制尚不完全清楚。普遍表达的转录异构体2 （UXT-V2）是一种α型前折叠蛋白，是一种与许多人类肿瘤相关的多功能转录因子，但其在病毒感染中的作用尚不清楚。本研究发现，异位表达UXT-V2可显著抑制HSV-2的复制，而敲除内源性表达的UXT-V2可促进HSV-2的增殖。进一步的分析表明，UXT-V2限制HSV-2的复制独立于其调节NF-κB的作用。在HSV-2感染或病毒糖蛋白B （gB）转染的细胞中，UXT-V2促进了gB的k48连锁泛素化，导致其通过蛋白酶体途径降解，从而抑制病毒复制。此外，我们发现UXT-V2与gB相互作用，招募E3连接酶TRIM21来促进gB的k48连锁泛素化。反过来，HSV-2在体外和小鼠体内都降低了UXT-V2蛋白的丰度，突出了HSV-2-宿主相互作用的复杂性。总之，我们的研究结果首次证明了UXT-V2具有抗hsv -2的作用，揭示了一种参与调节糖蛋白稳态的新型宿主免疫防御机制。

{"title":"Ubiquitously expressed transcript isoform 2 (UXT-V2) restricts HSV-2 replication by targeting glycoprotein B for degradation through ubiquitin-proteasome pathway","authors":"Chuntian Li , Yuncheng Li , Ranqing Cheng , Miaomiao Li , Mudan Zhang , Zhiyuan Zhu , Ping Yang , Qinxue Hu , Yalan Liu","doi":"10.1016/j.virs.2025.08.004","DOIUrl":"10.1016/j.virs.2025.08.004","url":null,"abstract":"<div><div>Herpes simplex virus 2 (HSV-2) is a major pathogen causing neonatal herpes and increasing the risk of human immunodeficiency virus 1 (HIV-1) infection. However, the mechanisms underlying host restriction of HSV-2 infection are still not fully understood. The ubiquitously expressed transcript isoform 2 (UXT-V2), an α-type prefoldin protein, functions as a versatile transcription factor associated with numerous human tumors, but its role in viral infection remains unclear. In this study, we found that ectopic expression of UXT-V2 significantly inhibited HSV-2 replication, while knockout of endogenously expressed UXT-V2 promoted HSV-2 proliferation. Further analysis revealed that UXT-V2 restricts HSV-2 replication independent of its role in regulating NF-κB. In the context of HSV-2 infection or in viral glycoprotein B (gB)-transfected cells, UXT-V2 facilitates K48-linked ubiquitination of gB, leading to its degradation via the proteasome pathway, thereby inhibiting viral replication. Furthermore, we identified that UXT-V2 interacts with gB, recruiting the E3 ligase TRIM21 to facilitate K48-linked ubiquitination of gB. HSV-2, in turn, reduces the abundance of UXT-V2 proteins both <em>in vitro</em> and in mice, highlighting the complexity of HSV-2-host interactions. Collectively, our findings, for the first time, demonstrate an anti-HSV-2 role of UXT-V2, unveiling a novel host immune defense mechanism involved in regulating glycoprotein homeostasis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 778-792"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001170","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}

引用次数: 0

SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy SNX10通过促进病毒进入和抑制病毒引发的自噬来增强HCoV-OC43感染。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.07.005

Haobin Li , Huiyi Guo , Binhao Rong , Haowei Li , Wenjiao Wu , Chan Yang , Shuwen Liu

The ongoing coronavirus epidemic, including the novel coronavirus (SARS-CoV-2), continues to pose a significant threat to global public health. Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions. This study identified sorting nexin 10 (SNX10) as a facilitator of replication of human coronavirus OC43 (HCoV-OC43), underscoring its potential as a novel antiviral target. The knockout of SNX10 significantly suppressed HCoV-OC43 replication both in vivo and in vitro. Immunoprecipitation-mass spectrometry (‌IP-MS) analysis identified the adaptor protein complex 2 subunit μ1 (AP2M1) as a direct interactor of SNX10. Specifically, SNX10 facilitates phosphorylation of the AP2M1, thereby enhancing clathrin-mediated viral endocytosis. Furthermore, subsequent binding and internalization assays revealed that SNX10 knockout significantly inhibits viral entry into host cells. Conversely, the reconstitution of SNX10 fully restored viral entry, thereby confirming the critical and indispensable role of SNX10 in pathogen internalization. Simultaneously, SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels, which in turn facilitated the release of the viral genome. Notably, the ablation of SNX10 was found to trigger autophagy activation during infection, thereby maintaining intracellular homeostasis. Additionally, it exerted autonomous antiviral effects through lysosomal degradation pathways. Collectively, these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization, viral genomic release, and host-pathogen equilibrium.

包括新型冠状病毒（COVID-19）在内的持续冠状病毒流行继续对全球公共卫生构成重大威胁。宿主靶点涉及病毒生命周期的多个阶段，并为治疗干预提供了多种机会。本研究确定了分选连接蛋白10 （SNX10）作为人冠状病毒OC43 （HCoV-OC43）复制的促进剂，强调了其作为新型抗病毒靶点的潜力。敲除SNX10显著抑制了HCoV-OC43在体内和体外的复制。免疫沉淀-质谱（IP-MS）分析发现，接头蛋白复合物2亚单位μ1 （AP2M1）是SNX10的直接相互作用因子。具体来说，SNX10促进AP2M1的磷酸化，从而增强网格蛋白介导的病毒内吞作用。此外，随后的结合和内化实验显示，SNX10基因敲除显著抑制病毒进入宿主细胞。相反，SNX10的重组完全恢复了病毒的进入，从而证实了SNX10在病原体内化中的关键和不可或缺的作用。同时，SNX10被鉴定为通过调节pH水平促进内体酸化的关键因子，从而促进病毒基因组的释放。值得注意的是，SNX10的消融被发现在感染期间触发自噬激活，从而维持细胞内稳态。此外，它通过溶酶体降解途径发挥自主抗病毒作用。总的来说，这些发现表明SNX10是病毒生命周期的关键调节因子，并强调了其作为多方面抗病毒候选药物的治疗潜力，能够同时抑制病毒内化、病毒基因组释放和宿主-病原体平衡。

{"title":"SNX10 enhances HCoV-OC43 infection by facilitating viral entry and inhibiting virus-triggered autophagy","authors":"Haobin Li , Huiyi Guo , Binhao Rong , Haowei Li , Wenjiao Wu , Chan Yang , Shuwen Liu","doi":"10.1016/j.virs.2025.07.005","DOIUrl":"10.1016/j.virs.2025.07.005","url":null,"abstract":"<div><div>The ongoing coronavirus epidemic, including the novel coronavirus (SARS-CoV-2), continues to pose a significant threat to global public health. Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions. This study identified sorting nexin 10 (SNX10) as a facilitator of replication of human coronavirus OC43 (HCoV-OC43), underscoring its potential as a novel antiviral target. The knockout of <em>SNX10</em> significantly suppressed HCoV-OC43 replication both <em>in vivo</em> and <em>in vitro</em>. Immunoprecipitation-mass spectrometry (‌IP-MS) analysis identified the adaptor protein complex 2 subunit μ1 (AP2M1) as a direct interactor of SNX10. Specifically, SNX10 facilitates phosphorylation of the AP2M1, thereby enhancing clathrin-mediated viral endocytosis. Furthermore, subsequent binding and internalization assays revealed that <em>SNX10</em> knockout significantly inhibits viral entry into host cells. Conversely, the reconstitution of SNX10 fully restored viral entry, thereby confirming the critical and indispensable role of SNX10 in pathogen internalization. Simultaneously, SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels, which in turn facilitated the release of the viral genome. Notably, the ablation of SNX10 was found to trigger autophagy activation during infection, thereby maintaining intracellular homeostasis. Additionally, it exerted autonomous antiviral effects through lysosomal degradation pathways. Collectively, these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization, viral genomic release, and host-pathogen equilibrium.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 755-768"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620767","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}

引用次数: 0

Antigenic and structural insights into Langya henipavirus attachment glycoprotein 亨尼帕病毒附着糖蛋白的抗原和结构研究。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.08.005

Yaohui Li , Xiaoyan Huang , Xiaodong Zai, Chenfeng Mao, Ruihua Li, Yamei Feng, Yue Zhang, Zhang Zhang, Jun Zhang, Junjie Xu

The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment (G) and fusion (F) glycoproteins with receptors on the cell surface. Langya henipavirus (LayV) was newly identified in China in 2022. The G proteins of LayV and Mojiang virus (MojV) exhibit high amino acid homology (86%), while they are located in a unique evolutionary clade within the Henipavirus genus. In this study, the crystal structure of the LayV G protein was resolved at a 3.37 Å resolution, revealing a head domain with six β-propeller-like domains distinct from other henipavirus G proteins, such as those of Nipah virus (NiV) and Hendra virus (HeV). Furthermore, the prominent loop in the center cavity of the LayV G protein showed unique structural features. In the ELISA and SPR assays, the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor. Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein. These antibodies exhibited strong reactivity against both LayV and MojV G proteins. However, only weak cross-reactivity was observed with other henipaviruses. Moreover, eight monoclonal antibodies targeting the LayV G protein were generated, two of which exhibited broad binding activity across different henipavirus G proteins. These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses

新型亨尼帕病毒琅琊亨尼帕病毒（LayV）于2022年在中国被发现。通过病毒附着(G)和融合(F)糖蛋白与细胞表面受体的相互作用，促进了亨尼帕病毒对宿主细胞的入侵。LayV病毒和漠江病毒（MojV）的G蛋白具有很高的氨基酸同源性（86%），它们位于亨尼帕病毒属中一个独特的进化分支。LayV G蛋白的晶体结构以3.4 Å的分辨率进行了解析，揭示了一个具有6个β-螺旋桨状结构域的头部结构域，并且没有糖基化修饰，这与尼帕病毒（NiV）和亨德拉病毒（HeV）等其他亨尼帕病毒G蛋白不同。此外，LayV G蛋白中心空腔中突出的环导致了独特的结构特征。LayV G蛋白不能与现有的亨尼帕病毒中和抗体或ephrin B2受体结合。小鼠的免疫原性研究表明，LayV G蛋白可引起强大的抗体反应。这些抗体对LayV和MojV G蛋白均表现出较强的反应性。但与其他亨尼帕病毒的交叉反应性较弱。这些发现强调需要针对LayV和相关的新型亨尼帕病毒定制疫苗和治疗方法。

{"title":"Antigenic and structural insights into Langya henipavirus attachment glycoprotein","authors":"Yaohui Li , Xiaoyan Huang , Xiaodong Zai, Chenfeng Mao, Ruihua Li, Yamei Feng, Yue Zhang, Zhang Zhang, Jun Zhang, Junjie Xu","doi":"10.1016/j.virs.2025.08.005","DOIUrl":"10.1016/j.virs.2025.08.005","url":null,"abstract":"<div><div>The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment (G) and fusion (F) glycoproteins with receptors on the cell surface. Langya henipavirus (LayV) was newly identified in China in 2022. The G proteins of LayV and Mojiang virus (MojV) exhibit high amino acid homology (86%), while they are located in a unique evolutionary clade within the <em>Henipavirus</em> genus. In this study, the crystal structure of the LayV G protein was resolved at a 3.37 Å resolution, revealing a head domain with six β-propeller-like domains distinct from other henipavirus G proteins, such as those of Nipah virus (NiV) and Hendra virus (HeV). Furthermore, the prominent loop in the center cavity of the LayV G protein showed unique structural features. In the ELISA and SPR assays, the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor. Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein. These antibodies exhibited strong reactivity against both LayV and MojV G proteins. However, only weak cross-reactivity was observed with other henipaviruses. Moreover, eight monoclonal antibodies targeting the LayV G protein were generated, two of which exhibited broad binding activity across different henipavirus G proteins. These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 5","pages":"Pages 769-777"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001138","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}

引用次数: 0

HBV and host metabolic crosstalk: Reprogramming pathways for viral replication and pathogenesis HBV和宿主代谢串扰：病毒复制和发病机制的重编程途径。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 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.

乙型肝炎病毒（HBV）通过对宿主代谢网络的战略性操纵建立慢性感染，驱动一系列肝脏病理，从肝炎到肝硬化和肝细胞癌。在机制上，HBV重编程核心代谢途径，包括糖酵解、三羧酸（TCA）循环、氧化磷酸化和脂质稳态，以促进其复制机制并逃避免疫监视。这篇综述系统地综合了目前关于hbv诱导的糖/脂代谢重布线的证据，特别强调了代谢界面上的病毒-宿主串扰如何维持病毒的发病机制。

引用次数: 0

Antisera and antivirals targeting the conserved domains in SARS-CoV-2 S2 subunit are effective against ACE2-using MERSr-CoVs with spillover potential 针对SARS-CoV-2 S2亚基保守结构域的抗血清和抗病毒药物对使用ace2的mers - cov有效，但具有溢出潜力。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 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

引用次数: 0

First identification of Tusavirus in calf intestinal tissue suggests interspecies transmission and genomic variation 首次在小牛肠道组织中发现的Tusavirus提示种间传播和基因组变异。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 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

引用次数: 0

Efficacy and safety of switching from lopinavir/ritonavir-based regimens to bictegravir/emtricitabine/tenofovir alafenamide in people living with HIV: A multicenter retrospective study HIV感染者从洛匹那韦/利托那韦转为比替重韦/恩曲他滨/替诺福韦阿拉那胺治疗的有效性和安全性：一项多中心回顾性研究

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 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.

在中国，大约13%的人类免疫缺陷病毒（HIV）（PLWH）感染者正在接受洛匹那韦/利托那韦（LPV/r）为主的治疗方案。这些PLWH通常有治疗失败或对一线依非韦伦方案不耐受的病史。考虑到相当大的药物负担和与LPV/r相关的不良反应，优化治疗对这一人群很重要。这项多中心回顾性研究旨在评估从LPV/r为基础的方案切换到比替格拉韦/恩曲他滨/替诺福韦阿拉那胺单片方案（BIC/FTC/TAF）的有效性和安全性。主要比较了改用BIC/FTC/TAF前后48周的病毒学抑制率（HIV-RNA < 40拷贝/mL）。同时评估CD4计数和代谢数据。在2021年1月至2023年12月期间，共招募了461名PLWH，其中92.2%为男性，中位年龄为38岁，中位抗逆转录病毒治疗持续时间为8年。在启动LPV/r之前，23.0%（106/461）有病毒学失败记录。在LPV/r治疗期间，18.9%（20/106）的患者出现病毒反弹。在所有参与者中，总体病毒学抑制率从切换前的94.6%显著增加到切换后的98.6% （P < 0.001）。值得注意的是，在先前有病毒学失败的参与者中，抑制率从81.1%显著提高到97.2% (P < 0.001)，而在没有病毒学失败史的参与者中没有显著差异（从98.6%到99.2%,P = 0.764）。中位甘油三酯水平从2.4 mmol/L降至1.8 mmol/L (P < 0.001)，而CD4计数无差异。这些研究结果表明，BIC/FTC/TAF对于从LPV/r为基础的方案转换为PLWH的有效和代谢有利的治疗选择，无论他们是否有先前的病毒学失败史。

{"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}

引用次数: 0

The coronavirus 3CL protease: Unveiling its complex host interactions and central role in viral pathogenesis 冠状病毒3CL蛋白酶：揭示其复杂的宿主相互作用及其在病毒发病中的核心作用。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 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.

3CL蛋白酶是冠状病毒中一种高度保守的酶，它通过精确切割多蛋白促进病毒复制，在病毒生命周期中起着至关重要的作用。除了其蛋白水解功能外，3CL蛋白酶还与宿主细胞蛋白参与复杂的相互作用，参与关键的细胞过程，如转录、翻译和核-胞质运输，有效地劫持细胞机制以促进病毒复制。此外，它会破坏先天免疫信号通路，抑制干扰素活性并切割抗病毒蛋白。此外，它调节宿主细胞死亡途径，包括焦亡和凋亡，干扰自噬和抑制应激颗粒的形成，以维持病毒感染和加剧病毒发病。本文综述了3CL蛋白酶协调病毒与宿主相互作用的分子机制，强调了其在冠状病毒发病机制中的核心作用，并强调了未来干预的潜在治疗靶点。

引用次数: 0

STAT5-c-Myc-axis regulates B cell metabolism in vaccinated individuals and COVID-19 recovered patients stat5 -c- myc轴调节接种疫苗个体和COVID-19康复患者的B细胞代谢。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 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.

SARS-CoV-2感染和疫苗接种都会引发免疫反应。前者导致自然获得性免疫，后者通过人工手段诱导主动免疫。然而，疫苗接种和感染的不同免疫效果及其潜在机制需要进一步澄清。在本研究中，我们比较了接种组和康复组外周血B细胞分化、血清学差异和BCR信号分子表达水平。免疫组表现出rbd特异性B细胞分化减少，记忆B细胞CD86信号强度降低，但B细胞BCR信号增强。在代谢信号方面，接种组pS6、c-Myc、pmTOR和pSTAT5表达水平升高，提示STAT5-c-Myc轴在调节B细胞代谢中发挥作用。此外，蛋白质组芯片分析显示，接种组血清中含有更高水平的针对SARS-CoV-2 N-Nter蛋白的IgG抗体和针对SARS-CoV-2 S1蛋白的IgA抗体。总之，这些发现表明，与康复组相比，接种疫苗组产生了更强大的冠状病毒特异性免疫反应，BCR信号传导和代谢活性增强。这些见解可能有助于优化SARS-CoV-2疫苗的设计。

{"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}

引用次数: 0

Thermal tolerance and inactivation of Ebola virus 埃博拉病毒的耐热性和灭活性。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 10.1016/j.virs.2025.07.004

Xiaoxiao Gao, Cheng Peng, Rongjuan Pei

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Virologica Sinica

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀