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

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

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
Available online: 31 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

Electronic Supplementary Material

10.1016j.virs.2026.07.012-ESM.docx
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