TY - JOUR T1 - Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages JF - bioRxiv DO - 10.1101/2022.02.01.478673 SP - 2022.02.01.478673 AU - Glenn Oliveira AU - Chantal B.F. Vogels AU - Ashley Zolfaghari AU - Sharada Saraf AU - Raphaelle Klitting AU - James Weger-Lucarelli AU - Carlos O. Ontiveros AU - Rimjhim Agarwal AU - Karla P. Leon AU - Konstantin A. Tsetsarkin AU - Eva Harris AU - Gregory D. Ebel AU - Shirlee Wohl AU - Nathan D. Grubaugh AU - Kristian G. Andersen Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/02/02/2022.02.01.478673.abstract N2 - RNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for lineage-specific fitness differences. We engineered a library of recombinant viruses representing twelve major Zika virus lineages and used them to measure replicative fitness within disease-relevant human primary cells and live mosquitoes. We found that two of these lineages conferred significant in vitro replicative fitness changes among human primary cells, but we did not find fitness changes in Aedes aegypti mosquitoes. Additionally, we found evidence for elevated levels of positive selection among five amino acid sites that define major Zika virus lineages. While our work suggests that Zika virus may have acquired several phenotypic changes during a short time scale, these changes were relatively moderate and do not appear to have enhanced virulence or transmission during the epidemic.Competing Interest StatementThe authors have declared no competing interest. ER -