Cell binding tropism of rat hepatitis E virus is a pivotal determinant of its zoonotic transmission to humans

• 成果类型: Article
• 署名作者: Guo, Hongbo; Xu, Jiaqi; Situ, Jianwen; Li, Chunyang; Wang, Xia; Hou, Yao; Yang, Guangde; Wang, Lingli; Ying, Dong; Li, Zheng; Wang, Zijie; Su, Jia; Ding, Yibo; Zeng, Dou; Zhang, Jikai; Ding, Xiaohui; Wu, Shusheng; Miao, Weiwei; Tang, Renxian; Lu, Yihan; Kong, Huihui; Zhou, Peng; Zheng, Zizheng; Zheng, Kuiyang; Pan, Xiucheng; Sridhar, Siddharth; Wang, Wehshi
• 署名单位: Xuzhou Medical University; University of Hong Kong; Xuzhou Medical University; Xiamen University; Chinese Academy of Sciences; Wuhan Institute of Virology, CAS; Guangzhou Laboratory; Fudan University; Chinese Academy of Agricultural Sciences; Harbin Veterinary Research Institute, CAAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13423
• DOI: 10.1073/pnas.2416255121
• 发表日期: 2024-11-05
• 关键词: entry; replication; mechanisms; EVOLUTION; monkeys; sites; hev

摘要

Classically, all hepatitis E virus (HEV) variants causing human infection belong to the genus Paslahepevirus (HEV- A). However, the increasing cases of rat HEV infection in humans since 2018 challenged this dogma, posing increasing health threats. Herein, we investigated the underlying mechanisms dictating the zoonotic potentials of different HEV species and their possible cross- protection relationships. rat HEV particles penetrated the cell membrane and entered human target cells postbinding. In contrast, ferret HEVVLPs showed marginal cell binding and entry ability, bat HEVVLPs and avian HEVVLPs exhibited no binding and entry potency. Structure- based three- dimensional mapping identified that the surface spike domain of rat HEV is crucial for cell binding. Antigenic cartography indicated that rat HEV exhibited partial cross- reaction with HEV- A. Intriguingly, sera of HEV- A infected patients or human HEV vaccine Hecolin (R) immunized individuals provided partial cross- protection against the binding of rat HEVVLPs to human target cells. In summary, the interactions between the viral capsid and cellular receptor(s) regulate the distinct zoonotic potentials of different HEV species. The systematic characterization of antigenic cartography and serological cross- reactivity of different HEV species provide valuable insights for the development of species- specific diagnosis and protective vaccines against zoonotic HEV infection.