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A single nonsynonymous mutation on ZIKV E protein-coding sequences leads to markedly increased neurovirulence in vivo

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Virologica Sinica 2022年第1期37卷 115-126页

作者： Zhihua Liu Yawei Zhang Mengli Cheng ningning Ge Jiayi Shu Zhiheng Xu Xiao Su Zhihua Kou Yigang Tong Chengfeng Qin Xia Jin Institut Pasteur of Shanghai Chinese Academy of SciencesShanghai200031China University of Chinese Academy of Sciences Beijing100049China Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghai201508China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing100071China State Key Laboratory of Molecular developmental Biology CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101China College of Life Science and Technology Beijing University of Chemical TechnologyBeijing100029China

Zika virus(ZIKV)can infect a wide range of tissues including the developmental brain of human *** specific viral genetic variants are linked to neuropathology is incompletely *** address this,we have intracranially serially passaged a clinical ZIKV isolate(SW01)in neonatal mice and discovered variants that exhibit markedly increased virulence and *** sequencing analysis combining with molecular virology studies revealed that a single 67d(Aspartic acid)to n(Asparagine)substitution on E protein is sufficient to confer the increased virulence and neurotropism in ***,virus clones with d67n mutation had higher viral production and caused more severe cytopathic effect(CPE)in human neural astrocytes U251 cells in vitro,indicating its potential neurological toxicity to human *** findings revealed that a single mutation d67n on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection may be important.

关键词： Zika virus(ZIKV) Envelope protein d67n Mutation neurovirulence

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