Identification of a novel ectromelia virus from rodent: Implications for use as an <i>in vivo</i> infection model for vaccine and antiviral research

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

August 2025

. doi: 10.1016/j.virs.2025.07.001

Citation: 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. Identification of a novel ectromelia virus from rodent: Implications for use as an in vivo infection model for vaccine and antiviral research .VIROLOGICA SINICA, 2025, 40(4) : 601-612. http://dx.doi.org/10.1016/j.virs.2025.07.001

一株新型鼠痘病毒的分离鉴定推动疫苗和抗病毒药物研究

霍恕婷 ^a ,
吴长城 ^a ,
祁振勇 ^a,b ,
孙洁伟 ^a ,
孟昕 ^a ,
宋敬东 ^a ,
张钟贤 ^a ,
靳立业 ^a,b ,
舒畅 ^a ,
林志峰 ^a,c ,
霍威邦 ^a ,
邓瑶 ^a ,
赵莉 ^a,, ,
李建东 ^a,, ,
谭文杰 ^a,,

a 中国疾病预防控制中心病毒病预防控制所, 传染病智能追踪与预警全国重点实验室;
b 新乡医学院公共卫生学院;
c 广西医科大学公共卫生学院, 广西艾滋病防治重点实验室

通讯作者： 赵莉, lizhao@ivdc.chinacdc.cn; 李建东, lijd@ivdc.chinacdc.cn; 谭文杰, tanwj@ivdc.chinacdc.cn
收稿日期： 2025-02-17
录用日期： 2025-07-03

摘要

鼠痘病毒（Ectromelia virus, ECTV）作为正痘病毒属成员，不仅是引起鼠痘的病原体，更是研究高致病性正痘病毒的关键替代模型。为填补目前鼠痘病毒毒株及基因组数据匮乏的研究空白，本研究首次从中国广东省野生啮齿动物中成功分离并鉴定出一株新型鼠痘病毒，命名为ECTV-China-C-Tan-GD01（ECTV-C-Tan-GD01）。通过纳米孔测序，作者成功获得一条包含完整末端反向重复序列的精确基因组，并首次阐明鼠痘病毒保守的发夹结构序列特征。该毒株基因组注释了199个特定的基因（其中正链编码91个，负链编码108个），其中EV159基因的移码突变（“G”碱基缺失）导致轴突导向蛋白C端截短，这些发现为鼠痘病毒基因组特征研究提供了全新见解。体外实验显示该毒株可感染鸡、金黄地鼠和人类细胞，具有广泛宿主嗜性。该毒株感染Vero/HeLa细胞后72小时即可达到复制高峰，早于BHK/CEF细胞（84小时）。小鼠体内攻毒实验证实其具有强大毒力（鼻内/足垫途径半数致死剂量小于1 PFU）和显著的肝脾组织趋向性。在抗病毒评价方面，单剂痘苗病毒天坛株或非复制型痘苗病毒天坛株均可诱导对该毒株的交叉保护；特考韦瑞、西多福韦和布林西多福韦能显著降低该病毒载量、活病毒滴度并改善病理损伤。本研究分离鉴定的ECTV-C-Tan-GD01为研究正痘病毒基因组演化和致病机制提供了宝贵的资源，也为研发正痘病毒疫苗和抗病毒药物提供了良好的体内评价模型。
- 鼠痘病毒
- , 正痘病毒
- , 基因组测序
- , 疫苗
- , 抗病毒药物

Identification of a novel ectromelia virus from rodent: Implications for use as an in vivo infection model for vaccine and antiviral research

Shuting Huo ^a ,
Changcheng Wu ^a ,
Zhenyong Qi ^a,b ,
Jiewei Sun ^a ,
Xin Meng ^a ,
Jingdong Song ^a ,
Zhongxian Zhang ^a ,
Liye Jin ^a,b ,
Chang Shu ^a ,
Zhifeng Lin ^a,c ,
Weibang Huo ^a ,
Yao Deng ^a ,
Li Zhao ^a,, ,
Jiandong Li ^a,, ,
Wenjie Tan ^a,,

a. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China;
b. School of Public Health, Xinxiang Medical University, Xinxiang, 453003, China;
c. Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, China

Corresponding author: Li Zhao, lizhao@ivdc.chinacdc.cn Jiandong Li, lijd@ivdc.chinacdc.cn Wenjie Tan, tanwj@ivdc.chinacdc.cn
Received Date: 17 February 2025
Accepted Date: 03 July 2025

Abstract

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.
- Ectromelia virus (ECTV)
- , Orthopoxvirus (OPV)
- , Genome sequencing
- , Vaccine
- , Antiviral

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