Virologica Sinica最新文献

英文中文

Black swans as sentinel species for the emergence of clade 2.3.4.4b highly pathogenic avian influenza (H5N1) in Shanghai, China, 2024 2024年中国上海2.3.4.4b支高致病性禽流感（H5N1）出现的黑天鹅作为前哨物种

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.07.008

Yuting Xu , Shihai Wu , Lei Ji , Jie Hu , Jin Wang , Ke Li , Yue Yuan , Gaojian Li , Guangjian Zhu , Panyu Hua , Qiuhong Miao , Hongxuan He , Guimei He

引用次数: 0

Genetic analysis of human adenovirus type 108 circulating in China during 2014–2024 2014-2024年中国流行人腺病毒108型的遗传分析

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.09.002

Jinjin Wang , Ling Jing , Yali Duan , Junhong Ai , Yun Zhu , Ran Wang , Xiangpeng Chen , Gen Lu , Yun Sun , Changchong Li , Rong Jin , Yunxiao Shang , Yixiao Bao , Shuhua An , Yunlian Zhou , Limin Ning , Baoping Xu , Yuhai Bi , Zhengde Xie

Human adenovirus type 108 (HAdV-108) has been detected in multiple countries, including China, and is associated with severe acute respiratory infection (ARI) in children, with reported fatalities. However, studies on HAdV-108 remain limited. This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China. From 2014 to 2024, 6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China, of which 505 (7.51%) tested positive for HAdV. The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis, which revealed that among 317 HAdV-isolated samples, 21 (6.62%) were identified as HAdV-108, ranking third after HAdV-114 and HAdV-7. Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever. Seven children had gastrointestinal symptoms, and two children without underlying diseases were diagnosed with severe pneumonia. Phylogenetic analysis of whole-genome sequences revealed distinct predominant epidemic branches between domestic and international strains, with one strain obtained in this study forming an independent branch. Hexon protein exhibited the fastest evolution rate, lowest identity, and greatest amino acid variability, while fiber protein displayed the slowest evolution rate, highest identity, and greatest conservation and stability. Compared with the earliest reported HAdV-108 strain, three amino acid deletions were identified in the RGD loop region of penton base protein, resulting in potential structural change. Recombination analysis identified five distinct recombination patterns. In vitro experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses. In summary, HAdV-108 has persistently circulated in China, causing severe ARIs and concurrent gastrointestinal manifestations. Cluster3 was the predominant epidemic branch in China. HAdV-108 exhibited significant intra-type genetic variation, with random and diverse recombination events.

已在包括中国在内的多个国家检测到人类腺病毒108型（HAdV-108），该病毒与儿童严重急性呼吸道感染（ARI）有关，并有死亡报告。然而，对HAdV-108的研究仍然有限。本研究旨在探讨中国ARI儿童HAdV-108的临床和遗传特征。2014 - 2024年，在中国北方和南方的10家医院收集了6720份ARI住院儿童的呼吸道样本，其中505例（7.51%）检测出hav阳性。对全基因组和3个主要衣壳蛋白基因进行扩增和生物信息学分析，结果显示，在317份hadv分离样本中，有21份（6.62%）鉴定为HAdV-108，排名第三，仅次于HAdV-114和HAdV-7。临床分析hadv -108阳性病例主要表现为咳嗽、发热。7名儿童出现胃肠道症状，2名无基础疾病的儿童被诊断为严重肺炎。全基因组序列的系统发育分析显示，国内菌株和国际菌株之间存在明显的优势流行分支，本研究获得的一个菌株形成了一个独立的分支。Hexon蛋白进化速度最快，同源性最低，氨基酸变异性最大，纤维蛋白进化速度最慢，同源性最高，保守性和稳定性最强。与最早报道的HAdV-108菌株相比，在戊基蛋白RGD环区发现了3个氨基酸缺失，可能导致结构变化。重组分析确定了五种不同的重组模式。体外实验表明，HAdV-108具有与其他C种腺病毒相当的增殖能力。综上所述，HAdV-108在中国持续流行，导致严重急性呼吸道感染和并发胃肠道症状。Cluster3是中国的优势流行分支。HAdV-108表现出显著的型内遗传变异，重组事件随机多样。

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引用次数: 0

Seasonal dynamics of hedgehog-borne ticks and severe fever with thrombocytopenia syndrome virus in Beijing's urban parks 北京城市公园刺猬蜱和发热伴血小板减少综合征病毒的季节动态

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.10.005

Chunzheng Li , Hongyue Li , Yuanchi Ye , Lianglong Zhu , Aihua Zheng , Xing Zhang

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne pathogen, has caused a rising number of human cases in the urban-rural fringe of Beijing since 2021. This study explores the seasonal dynamics of hedgehog-associated ticks and SFTSV transmission in urban parks of Beijing. Surveys across six parks revealed distinct activity patterns: adult Haemaphysalis longicornis peaked in summer, while nymphs dominated spring and autumn. All collected H. longicornis belonged to parthenogenetic populations. A near-complete SFTSV genome (C4 strain) was identified in a tick collected from Taoranting Park, suggesting multiple viral introductions into Beijing. Serological analysis showed that > 50% of hedgehogs carried SFTSV-neutralizing antibodies in spring; yet seropositivity declined markedly in summer and autumn, indicating recurrent infections and implicating hedgehogs as potential reservoirs. These findings reveal an urban SFTSV transmission cycle maintained by hedgehogs and parthenogenetic H. longicornis, emphasizing the urgency of enhanced surveillance and public health interventions to curb urban zoonotic risks.

严重发热伴血小板减少综合征病毒（SFTSV）是一种新出现的蜱传病原体，自2021年以来，在北京城乡边缘地区造成的人间病例数量不断上升。本研究旨在探讨北京城市公园刺猬相关蜱的季节动态和SFTSV传播。对六个公园的调查显示了不同的活动模式：成年长角血蜱在夏季达到高峰，而若虫在春季和秋季占主导地位。所有收集到的长角蜱属孤雌种群。在陶然亭公园采集的蜱中鉴定出一个接近完整的SFTSV基因组（C4株），提示该病毒曾多次传入北京。血清学分析显示，春季有50%的刺猬携带sftsv中和抗体；然而，在夏季和秋季，血清阳性率明显下降，表明反复感染，暗示刺猬是潜在的宿主。这些发现揭示了刺猬和孤雌长角锥虫维持的城市SFTSV传播周期，强调了加强监测和公共卫生干预以遏制城市人畜共患病风险的紧迫性。

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引用次数: 0

Synthetic genomics-based generation of the tick-borne encephalitis virus Siberian subtype prototype strain and E51K-attenuated variant for vaccine development and antiviral screening 基于合成基因组学的蜱传脑炎病毒西伯利亚亚型原型株和e51k减毒变种疫苗研制和抗病毒筛选

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/j.virs.2025.09.010

Tolganay Kulatay , Elena Sedova , Alexander Shevtsov , Gulzat Zauatbayeva , Bakytkali Ingirbay , Viktoriya Keyer , Zhanar Shakhmanova , Maral Zhumabekova , Yergali Abduraimov , Aralbek Rsaliyev , Nurgul Sikhayeva , Irina Kozlova , Mikhail Zaripov , Alexandr V. Shustov

Tick-borne encephalitis virus (TBEV) is a re-emerging pathogen in Kazakhstan, where the increasing risk of its spread underscores the need for improved healthcare preparedness, including the development of local vaccines. However, the absence of reference TBEV strains in the country presented a major challenge. To address this, we generated a prototype strain (Vasilchenko) of the Siberian TBEV genotype, predominant in Kazakhstan, using synthetic genome and molecular infectious clone technology. A DNA-launched TBEV molecular clone was assembled from DNA fragments, enabling virus rescue upon plasmid transfection. During the propagation of the post-transfection virus in cell culture, a single amino acid substitution (E51K) in the envelope protein emerged, resulting in a 100-fold increase in the titer of the mutant variant. In vivo, this mutation significantly attenuated virulence: while wild-type TBEV caused 100% mortality in BALB/c mice, the E51K variant was non-lethal and exhibited reduced viremia, suggesting impaired neuroinvasiveness. To further exploit this attenuated, high-titer virus, we developed a GFP-expressing reporter TBEV variant. Using this reporter system, we demonstrated that favipiravir possesses antiviral activity against TBEV, with inhibitory concentrations within a pharmacologically relevant range. In conclusion, synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections. The E51K mutation enhances viral replication in vitro while attenuating pathogenicity in vivo, and the derived reporter virus is suitable for antiviral compound screening.

在哈萨克斯坦，蜱传脑炎病毒（TBEV）是一种重新出现的病原体，其传播风险日益增加，这突出表明需要改进卫生保健准备，包括开发当地疫苗。然而，该国缺乏参考的热带病病毒菌株是一项重大挑战。为了解决这个问题，我们利用合成基因组和分子感染克隆技术，生成了一株西伯利亚TBEV基因型的原型菌株（Vasilchenko），该基因型在哈萨克斯坦占主导地位。利用DNA片段组装DNA启动的TBEV分子克隆，使病毒在质粒转染后获救。转染后病毒在细胞培养中繁殖时，包膜蛋白中出现一个氨基酸替换（E51K），导致突变体的滴度增加100倍。在体内，这种突变显著降低了毒力：野生型TBEV在BALB/c小鼠中导致100%的死亡率，而E51K变体非致命性，表现出病毒血症减少，表明神经侵袭性受损。为了进一步利用这种减毒的高滴度病毒，我们开发了一种表达gfp的报告病毒TBEV变体。利用该报告系统，我们证明了favipiravir对TBEV具有抗病毒活性，其抑制浓度在药理学相关范围内。总之，合成基因组学能够产生参考的TBEV菌株，以补充哈萨克斯坦的收藏。E51K突变在体外增强病毒复制，在体内减弱致病性，衍生的报告病毒适合抗病毒化合物筛选。

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引用次数: 0

Issue Cover 覆盖问题

IF 4 3区医学 Q1 Medicine

Virologica Sinica

Pub Date : 2025-10-01 DOI: 10.1016/S1995-820X(25)00142-7

引用次数: 0

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。

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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。

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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。

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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

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