Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages

dc.contributor.authorOliveira, Glennen
dc.contributor.authorVogels, Chantal B. F.en
dc.contributor.authorZolfaghari, Ashleyen
dc.contributor.authorSaraf, Sharadaen
dc.contributor.authorKlitting, Raphaelleen
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorLeon, Karla P.en
dc.contributor.authorOntiveros, Carlos O.en
dc.contributor.authorAgarwal, Rimjhimen
dc.contributor.authorTsetsarkin, Konstantin A.en
dc.contributor.authorHarris, Evaen
dc.contributor.authorEbel, Gregory D.en
dc.contributor.authorWohl, Shirleeen
dc.contributor.authorGrubaugh, Nathan D.en
dc.contributor.authorAndersen, Kristian G.en
dc.description.abstractZika virus was introduced to the Western Hemisphere, spread rapidly, and led to the 2015-2016 Zika epidemic and a rise in congenital microcephaly. It remains unclear whether Zika virus evolved to become more transmissible directly before or during the epidemic. To investigate whether Zika evolved to become more transmissible, we engineered a library of recombinant viruses that represent twelve major Zika virus lineages that circulated throughout the Americas. We measured the replicative fitness of each of these lineages by infecting live mosquitoes and human cells that are relevant for disease or transmission. We found that two of the lineages, one that dominated Central America and another that existed mostly in the Caribbean, appear to replicate more efficiently in human cells. While the fitness changes do not appear to have significant effects on the 2015-2016 Zika epidemic, our analysis suggests Zika virus evolved at least twice during this outbreak. Monitoring the phenotypic evolution during the course of an outbreak can help control spread and mitigate disease. We believe this framework can be applied to study phenotypic evolution during future epidemics caused by emerging RNA viruses. 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 transmission during the epidemic.en
dc.description.notesC.B.F.V. is supported by NWO Rubicon (no. 019.181EN.004). K.G.A. is a Pew Biomedical Scholar and is supported by NIH NCATS CTSA L1TR002550, NIAID R21AI137690, and The Ray Thomas Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipNWO Rubicon [019.181EN.004]; NIH NCATS CTSA; NIAID [L1TR002550]; Ray Thomas Foundation; [R21AI137690]en
dc.description.versionPublished versionen
dc.publisherPublic Library of Scienceen
dc.rightsCC0 1.0 Universal Public Domain Dedicationen
dc.subjectsingle mutationen
dc.titleGenomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineagesen
dc.title.serialPLOS Neglected Tropical Diseasesen
dc.typeArticle - Refereeden
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