The trajectory of the emergence of Zika virus (ZIKV) into the Americas remains unclear. Here, the authors find that four mutations originated before ZIKV introduction to the Americas are direct reversions of previous mutations that accompanied spread many decades ago from ZIKV’s native Africa to Asia, and show in experimental infections of mosquitoes, human cells, and mice that the original mutations reduced fitness for urban transmission, while the reversions restored fitness, likely increasing epidemic risk.
- Jianying Liu
- Yang Liu
- Scott C. Weaver
