The pre-existing cellular immunity to Japanese encephalitis virus heterotypically protects mice from Zika virus infection

Weihong Zhang; Yongfen Xu; Fanfan Zhao; Marion Tarbe; Shuru Zhou; Weihong Wang; Shengyuan Zhang; Wei Zhang; Qiuping Xu; Lina Shi; Feng Yuan; Xinwen Lin; Shuai Liu; Jing Sun; Jincun Zhao; Yaling Yang; Xiaozhen Liang; Jin Zhong; Gang Long; Chengfeng Qin; Qibin Leng; Hong Tang

doi:10.1016/j.scib.2019.11.006

The pre-existing cellular immunity to Japanese encephalitis virus heterotypically protects mice from Zika virus infection

Sci Bull (Beijing). 2020 Mar 15;65(5):402-409. doi: 10.1016/j.scib.2019.11.006. Epub 2019 Nov 6.

Authors

Weihong Zhang¹, Yongfen Xu², Fanfan Zhao³, Marion Tarbe², Shuru Zhou⁴, Weihong Wang⁵, Shengyuan Zhang⁵, Wei Zhang², Qiuping Xu³, Lina Shi³, Feng Yuan³, Xinwen Lin³, Shuai Liu³, Jing Sun⁶, Jincun Zhao⁶, Yaling Yang⁷, Xiaozhen Liang², Jin Zhong², Gang Long², Chengfeng Qin⁸, Qibin Leng⁹, Hong Tang¹⁰

Affiliations

¹ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
³ CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
⁵ CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁶ State Key Laboratory of Respiratory Diseases, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510095, China.
⁷ Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
⁸ Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
⁹ CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; State Key Laboratory of Respiratory Diseases, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510095, China. Electronic address: [email protected].
¹⁰ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: [email protected].

PMID: 36659231
DOI: 10.1016/j.scib.2019.11.006

Abstract

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related flaviviruses, ZIKV circulates in the population that has been JEV vaccinated in Southeast Asian countries. This alerts that a pre-existing immunity to JEV would impact ZIKV infection and/or pathogenesis. Herein we showed that the pre-existing immunity to JEV SA14-14-2 vaccination provided an ample protection against non-lethal or lethal dose of ZIKV infection in mice. This was in sharp contrast to the passive immunization of JEV antibodies, which failed to affect ZIKV infection or pathogenesis in mice, albeit these antibodies exhibited cross-reactivity and antibody dependent enhancement (ADE) of ZIKV infection in vitro. Furthermore, we determined that JEV vaccine-elicited CD8⁺ T cells were required to mediate the heterotypic protection of ZIKV infection, which cross-reacted to ZIKV E and NS5 antigens (E_294-302 and NS5_2839-2848). Adoptive transfer of these CD8⁺ T cells could partially protect the mice from ZIKV challenge. Therefore, although short of epidemiological evidence, these results suggested that cross-reactive CD8⁺ T cells activated by JEV vaccination could protect potential ZIKV infection in human populations.

Keywords: CD8(+) T; Cross protection; Japanese encephalitis virus; Zika virus.