RT Journal Article SR Electronic T1 Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.02.01.478673 DO 10.1101/2022.02.01.478673 A1 Glenn Oliveira A1 Chantal B.F. Vogels A1 Ashley Zolfaghari A1 Sharada Saraf A1 Raphaelle Klitting A1 James Weger-Lucarelli A1 Carlos O. Ontiveros A1 Rimjhim Agarwal A1 Karla P. Leon A1 Konstantin A. Tsetsarkin A1 Eva Harris A1 Gregory D. Ebel A1 Shirlee Wohl A1 Nathan D. Grubaugh A1 Kristian G. Andersen YR 2022 UL http://biorxiv.org/content/early/2022/02/02/2022.02.01.478673.abstract AB 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.