Summary Paragraph
Mosquito-borne viruses have recently spread globally, with major impacts on human health. 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. For the first time, severe clinical manifestations, including Guillain Barré syndrome and congenital defects to the fetus of pregnant women, were detected. 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. However, the reasons for the sudden emergence of ZIKV remain incompletely understood. Accumulating evidence on other arboviruses like chikungunya and West Nile suggest the likelihood that viral mutations could be determinants of change in ZIKV transmission efficiency responsible for efficient spread. Using evolutionary analyses, we determined that four mutations, which occurred just before ZIKV introduction to the Americas, represent direct reversions of previous mutations that accompanied spread many decades ago from ZIKV’s native Africa to Asia and early circulation there. Experimental infections of mosquitoes, human cells, and mice with ZIKV strains with and without these mutations demonstrated that the original mutations reduced fitness for urban transmission, while the reversions restored fitness, increasing epidemic risk. Our findings help to explain the recent ZIKV emergence and underscore the major yet unpredictable impacts of founder effects and genetic drift on viral emergence. Because they involve random mutations that become fixed in a population when it undergoes bottlenecks during geographic spread and inefficient transmission, founder effects and other forms of drift can limit the ability of mosquito-borne viruses like ZIKV to emerge. Furthermore, their stochastic nature limits our ability to predict epidemics.
Competing Interest Statement
The authors have declared no competing interest.