Genetic heterogeneity and pathogenic potential of historical Crimean-Congo hemorrhagic fever virus isolates in China

Abulimiti Moming; Yuan Bai; Qiong Zhu; Jiayin Jin; Yaohui Fang; Shouwei Huang; Qiaoli Wu; Zhengyuan Su; Guoyu Zhao; Shuang Tang; Manli Wang; Zhihong Hu; Yujiang Zhang; Fei Deng; Shu Shen

doi:10.1016/j.virs.2026.07.012

August 2026

. doi: 10.1016/j.virs.2026.07.012

Citation: Abulimiti Moming, Yuan Bai, Qiong Zhu, Jiayin Jin, Yaohui Fang, Shouwei Huang, Qiaoli Wu, Zhengyuan Su, Guoyu Zhao, Shuang Tang, Manli Wang, Zhihong Hu, Yujiang Zhang, Fei Deng, Shu Shen. Genetic heterogeneity and pathogenic potential of historical Crimean-Congo hemorrhagic fever virus isolates in China .VIROLOGICA SINICA, 2026, 41(4) : 832-841. http://dx.doi.org/10.1016/j.virs.2026.07.012

中国克里米亚-刚果出血热病毒历史分离株的遗传多样性与致病性研究

阿布力米提·莫明 ^a,b,c ,
白源 ^a ,
朱琼 ^a ,
靳佳音 ^a ,
方耀辉 ^a ,
黄守卫 ^a ,
吴巧丽 ^a ,
苏正元 ^a ,
赵国玉 ^b,c ,
唐霜 ^a ,
王曼丽 ^a ,
胡志红 ^a ,
张渝疆 ^b,c,, ,
邓菲 ^a,, ,
沈姝 ^a,c,,

a 中国科学院武汉病毒研究所, 国家病毒资源库, 高致病性病毒与生物安全全国重点实验室, 湖北, 武汉, 430071;
b 新疆维吾尔自治区疾病预防控制中心, 新疆, 乌鲁木齐, 830002;
c 新疆病媒传染病重点实验室, 新疆, 乌鲁木齐, 830002

通讯作者： 张渝疆, xjsyzhang@163.com; 邓菲, df@wh.iov.cn; 沈姝, shenshu@wh.iov.cn
收稿日期： 2025-12-26
录用日期： 2026-07-28

摘要

克里米亚-刚果出血热病毒（CCHFV）对公共卫生构成了重大威胁。在中国，CCHFV已流行数十年，然而，关于流行毒株的全面遗传多样性和致病潜力仍缺乏详细描述，这阻碍了风险评估和对策的制定。在本研究中，我们复苏了24株历史CCHFV分离株（1966-2004年）进行全基因组测序，并对其系统发育、体外感染性和体内致病性进行了比较分析。系统发育分析揭示了高度的遗传异质性，鉴定出L片段的7种基因型、M片段的9种基因型（包括一种新型亚洲4基因型）以及S片段的9种基因型。氨基酸突变分析显示，糖蛋白（GP）的黏蛋白样结构域（MLD）的突变率最高。在体外实验中，亚洲2型（75024）和亚洲3型（79121M18）毒株在猴源、仓鼠源和人源细胞系中表现出强的复制能力，而蜱源亚洲 4型毒株（BA04032）则表现出感染性减弱。在C57BL/6小鼠中，所有毒株均诱导了病毒复制和特异性抗体反应（IgM和IgG），导致肝脏、脾脏和肾脏出现轻度至中度病理损伤。在IFNAR^-/^-小鼠中，毒力因基因型而异：亚洲2型和亚洲3型毒株高度致死（LD50 < 1 TCID50），亚洲1型毒株具有中等毒力（LD50 = 142.5 TCID50），而亚洲4型则表现出非典型、非剂量依赖性的死亡率。综上所述，我们的工作报告了一种新型亚洲4基因型，并提示了中国CCHFV毒株和谱系相关的毒力差异，为基因型特异性监测和针对性对策的制定提供了基础。
- 克里米亚-刚果出血热病毒
- , 遗传多样性
- , 亚洲4型基因型
- , 致病性

Genetic heterogeneity and pathogenic potential of historical Crimean-Congo hemorrhagic fever virus isolates in China

Abulimiti Moming ^a,b,c ,
Yuan Bai ^a ,
Qiong Zhu ^a ,
Jiayin Jin ^a ,
Yaohui Fang ^a ,
Shouwei Huang ^a ,
Qiaoli Wu ^a ,
Zhengyuan Su ^a ,
Guoyu Zhao ^b,c ,
Shuang Tang ^a ,
Manli Wang ^a ,
Zhihong Hu ^a ,
Yujiang Zhang ^b,c,, ,
Fei Deng ^a,, ,
Shu Shen ^a,c,,

a. State Key Laboratory of Virology and Biosafety, National Virus Resource Centre, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
b. Center for Disease Control and Prevention of Xinjiang Uyghur Autonomous Region, Urumqi 830002, China;
c. Xinjiang Key Laboratory of Vector-borne Infectious Diseases, Urumqi 830002, China

Corresponding author: Yujiang Zhang, xjsyzhang@163.com Fei Deng, df@wh.iov.cn Shu Shen, shenshu@wh.iov.cn
Received Date: 26 December 2025
Accepted Date: 28 July 2026

Abstract

The Crimean-Congo hemorrhagic fever virus (CCHFV) poses a significant public health threat. In China, CCHFV has been circulating for decades, yet the genomic diversity and pathogenic potential of the circulating strains remain poorly characterized, hindering risk assessment and countermeasure development. In this study, we recovered 24 historical CCHFV strains isolated between 1966 and 2004 from humans, ticks and jerboas in Xinjiang Uyghur Autonomous Region of China. Whole-genome sequencing was performed, followed by comprehensive analyses of their phylogenetic relationships, in vitro infectivity and in vivo pathogenicity. Phylogenetic analyses revealed high genetic heterogeneity, identifying seven genotypes for the L segment, nine for the M segment (including a novel Asia 4 genotype), and nine for the S segment. Amino acid mutation analysis revealed that the mucin-like domain (MLD) of the glycoprotein (GP) exhibited the highest mutation rate, contributing substantially to sequence diversity. In vitro, Asia 2 (75024) and Asia 3 (79121M18) strains exhibited robust replication in monkey-, hamster-, and human-derived cell lines. In C57BL/6 mice, all four representative strains induced viral replication and specific antibody responses (IgM and IgG), causing mild to moderate pathological damage in the liver, spleen, and kidneys. In IFNAR^-/- mice, virulence varied markedly among representative strains: Asia 2 and Asia 3 strains were highly lethal (LD₅₀ < 1 TCID₅₀), Asia 1 was moderately virulent (LD₅₀ = 142.5 TCID₅₀), and Asia 4 exhibited atypical, non-dose-dependent mortality. Collectively, our work reports a novel Asia 4 genotype and suggests strain- and lineage-associated differences in virulence for CCHFV in China, providing critical insights for surveillance and targeted countermeasure development.
- Crimean-Congo hemorrhagic fever virus (CCHFV)
- , Genetic diversity
- , Asia 4 genotype
- , Pathogenicity

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Electronic Supplementary Material

10.1016j.virs.2026.07.012-ESM.docx