Substantial spillover burden of rat hepatitis E virus in humans

Zihao Chen, Lifeng Wang, Yongde Zhang, Guanghui Li, Jiaxiang Yin, Jingyan Fan, Tianxu Liu, Han Wu, Yue Huang, Wenhui Huang, Donglin Liu, Xiaoxiang Zheng, Xia Zang, Xingcheng Huang, Liuwei Song, Shunhua Wen, Jiayu Li, Dong Ying, Mujin Fang, Yingbin Wang, Ting Wu, Siddharth Sridhar, Jun Zhang, Ningshao Xia (), Lin Wang (), Yihan Lu () and Zizheng Zheng ()
Additional contact information
Zihao Chen: Xiamen University
Lifeng Wang: Menghai County People’s Hospital
Yongde Zhang: Menghai County Center for Disease Control and Prevention
Guanghui Li: Xiamen University
Jiaxiang Yin: Dali University
Jingyan Fan: Xiamen University
Tianxu Liu: Peking University Health Science Center
Han Wu: Fudan University
Yue Huang: Xiamen University
Wenhui Huang: Xiamen University
Donglin Liu: Jiangsu Provincial Center for Disease Control and Prevention
Xiaoxiang Zheng: Jiangsu Provincial Center for Disease Control and Prevention
Xia Zang: Jiangsu Provincial Center for Disease Control and Prevention
Xingcheng Huang: Xiamen University
Liuwei Song: Xiamen
Shunhua Wen: Xiamen
Jiayu Li: Xiamen
Dong Ying: Xiamen University
Mujin Fang: Xiamen University
Yingbin Wang: Xiamen University
Ting Wu: Xiamen University
Siddharth Sridhar: Pokfulam
Jun Zhang: Xiamen University
Ningshao Xia: Xiamen University
Lin Wang: Peking University Health Science Center
Yihan Lu: Fudan University
Zizheng Zheng: Xiamen University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The emergence of Rocahepevirus ratti genotype 1 (rat hepatitis E virus; rat HEV) in humans presents an unprecedented threat; however, the risk of rat HEV transmission to humans is not well understood. Here, we report the “Distinguishing Antibody Response Elicitation (DARE)” method, which distinguishes exposure to rat HEV. We use four study sets from China for large-scale population analysis: set 1 (hospital visit) and set 3 (ALT abnormality) from Yunnan province, a biodiversity hotspot, and set 2 (received physical examination) and set 4 (ALT abnormality) from Jiangsu province, a non-hotspot control region. rat HEV exposure risk is significantly higher in Yunnan, with 21.97% (190 of 865) in set 1 and 13.97% (70 of 501) in set 3, compared to 0.75% (9 of 1196) in Jiangsu’s set 2. Six spillover infections for rat HEV are identified in set 1, with one case of abnormal ALT. The rat-1d strains carried by rats are closely related to those human infections. Our study reveals the substantial spillover burden posed by rat HEV in biodiversity hotspots and highlights the utility of DARE method for proactive surveillance of public health emergencies.

Date: 2025
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DOI: 10.1038/s41467-025-59345-6

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