A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission

Significance ZIKV has “silently” circulated without causing severe diseases for decades since its discovery in 1947. Our study demonstrated that ZIKV acquired an evolutionary mutation in viral envelope gene (E-V473M) that increases virulence, maternal-to-fetal transmission during pregnancy, and viremia in nonhuman primates to facilitate urban transmission since 2013, which may be responsible for the recent emergence and severe diseases. Our results underscore the potential that high genetic mutation frequencies during arbovirus replication and transmission between mosquito and vertebrate hosts could lead to emergence and reemergence of those pathogens. Understanding the mechanisms of emergence and enhanced transmission is essential to detect and respond to future arbovirus outbreaks.