A mutation-mediated evolutionary adaptation of Zika virus in mosquito and mammalian host

Xi Yu, Chao Shan, Yibin Zhu, Enhao Ma, Jinglin Wang, Penghua Wang, Pei Yong Shi, Gong Cheng

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Zika virus (ZIKV) caused millions of infections during its rapid and expansive spread from Asia to the Americas from 2015 to 2017. Here, we compared the infectivity of ZIKV mutants with individual stable substitutions which emerged throughout the Asian ZIKV lineage and were responsible for the explosive outbreaks in the Americas. A threonine (T) to alanine (A) mutation at the 106th residue of the ZIKV capsid (C) protein facilitated the transmission by its mosquito vector, as well as infection in both human cells and immunodeficient mice. A mechanistic study showed that the T106A substitution rendered the C a preferred substrate for the NS2B-NS3 protease, thereby facilitating the maturation of structural proteins and the formation of infectious viral particles. Over a complete "mosquito-mouse-mosquito" cycle, the ZIKV C-T106A mutant showed a higher prevalence of mosquito infection than did the preepidemic strain, thus promoting ZIKV dissemination. Our results support the contribution of this evolutionary adaptation to the occasional widespread reemergence of ZIKV in nature.

Original languageEnglish (US)
Article numbere2113015118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number42
DOIs
StatePublished - Oct 19 2021

Keywords

  • Evolutionary adaptation
  • Host
  • Mosquito
  • Mutation
  • Zika virus

ASJC Scopus subject areas

  • General

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