Virologica Sinica最新文献

英文中文

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。

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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。

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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

Virome diversity in small mammals from south China: Insights into virus evolution, transmission, and ecology 华南小型哺乳动物的病毒群多样性：对病毒进化、传播和生态学的见解。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 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。

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引用次数: 0

Identification of a novel ectromelia virus from rodent: Implications for use as an in vivo infection model for vaccine and antiviral research 从啮齿动物中鉴定出一种新的鼠爪病毒：用于疫苗和抗病毒研究的体内感染模型的意义。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 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。

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引用次数: 0

SARS-CoV-2-encoded miR-nsp3-3p promotes pulmonary fibrosis by inhibiting expression of ALCAM sars - cov -2编码的miR-nsp3-3p通过抑制ALCAM的表达促进肺纤维化。

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 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.

来自病毒的microrna （miRNAs）已在体液中被检测到，并且已知可调节宿主基因的表达。最近的证据表明，sars - cov -2编码的mirna可能导致肺部疾病。肺纤维化是SARS-CoV-2感染患者住院期间或出院后的重要并发症，但其潜在机制尚未完全阐明。在这里，我们报道了sars - cov -2编码的miRNA miR-nsp3-3p，通过抑制活化的白细胞粘附分子（ALCAM）的表达和促进上皮-间质转化（EMT）来促进宿主肺纤维化。首先，我们在临床标本中检测了miR-nsp3-3p，发现重症/危重患者的咽拭子和肺泡灌洗液中miR-nsp3-3p与对照组或轻/中度患者相比显著增加。我们进一步发现腺相关病毒（adeno-associated virus， AAV）-nsp3感染可诱导BALB/c小鼠肺纤维化，而miR-nsp3-3p拮抗剂可逆转这一现象，并且发现ALCAM是miR-nsp3-3p的靶基因。过表达miR-nsp3-3p可抑制ALCAM的表达，促进肺上皮细胞的EMT。此外，ALCAM过表达可以逆转mir -nsp3-3p诱导的EMT和纤维化。这些发现突出了sars - cov -2编码的mirna在促进肺部疾病病理进展中的重要作用，并为病毒mirna与宿主病理之间的相互作用提供了新的见解。

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IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-08-01 DOI: 10.1016/S1995-820X(25)00108-7

引用次数: 0

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