Role of mutational reversions and fitness restoration in Zika virus spread to the Americas

Jianying Liu, Yang Liu, Chao Shan, Bruno T.D. Nunes, Ruimei Yun, Sherry Haller, Grace H. Rafael, Sasha Azar, Clark R. Andersen, Kenneth Plante, Nikos Vasilakis, Pei-Yong Shi, Scott C. Weaver

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Zika virus (ZIKV) emerged from obscurity in 2013 to spread from Asia to the South Pacific and the Americas, where millions of people were infected, accompanied by severe disease including microcephaly following congenital infections. Phylogenetic studies have shown that ZIKV evolved in Africa and later spread to Asia, and that the Asian lineage is responsible for the recent epidemics in the South Pacific and Americas. However, the reasons for the sudden emergence of ZIKV remain enigmatic. Here we report evolutionary analyses that revealed four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied earlier spread from Africa to Asia and early circulation there. Our experimental infections of Aedes aegypti mosquitoes, human cells, and mice using ZIKV strains with and without these mutations demonstrate that the original mutations reduced fitness for urban, human-amplifed transmission, while the reversions restored fitness, increasing epidemic risk. These findings include characterization of three transmission-adaptive ZIKV mutations, and demonstration that these and one identified previously restored fitness for epidemic transmission soon before introduction into the Americas. The initial mutations may have followed founder effects and/or drift when the virus was introduced decades ago into Asia.

Original languageEnglish (US)
Article number595
JournalNature communications
Issue number1
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'Role of mutational reversions and fitness restoration in Zika virus spread to the Americas'. Together they form a unique fingerprint.

Cite this