Abstract

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.

Highlights

  • 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

  • ZIKV continued to spread to most countries in the Americas with the continued association with Guillain Barré syndrome (GBS) and congenital Zika syndrome (CZS), leading the World Health Organization to declare in 2016 a Public Health Emergency of International Concern

  • The first evidence supporting this adaptive evolution hypothesis for ZIKV came from studies of an A188V amino acid substitution in the nonstructural protein 1 (NS1-A188V) first detected in 2013, just before ZIKV spread to the South Pacific and the Americas

Read more

Summary

Introduction

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. We report the results of further ZIKV phylogenetic analyses that reveal that four amino acid substitutions that preceded introductions into the South Pacific and the Americas represent direct reversions of previous mutations that occurred during or soon after ZIKV was introduced long ago into Asia from Africa. These reversions restored fitness declines for urban transmission that resulted from the initial mutations, increasing epidemic potential

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call