Rapid Evolution of Enhanced Zika Virus Virulence during Direct Vertebrate Transmission Chains

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dc.contributor.authorRiemersma, Kasen K.en
dc.contributor.authorJaeger, Anna S.en
dc.contributor.authorCrooks, Chelsea M.en
dc.contributor.authorBraun, Katarina M.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorEbel, Gregory D.en
dc.contributor.authorFriedrich, Thomas C.en
dc.contributor.authorAliota, Matthew T.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-07-30T17:13:23Zen
dc.date.available2021-07-30T17:13:23Zen
dc.date.issued2021-04en
dc.description.abstractZika virus (ZIKV) has the unusual capacity to circumvent natural alternating mosquito-human transmission and be directly transmitted human to human via sexual and vertical routes. The impact of direct transmission on ZIKV evolution and adaptation to vertebrate hosts is unknown. Here, we show that molecularly barcoded ZIKV rapidly adapted to a mammalian host during direct transmission chains in mice, coincident with the emergence of an amino acid substitution previously shown to enhance virulence. In contrast, little to no adaptation of ZIKV to mice was observed following chains of direct transmission in mosquitoes or alternating host transmission. Detailed genetic analyses revealed that ZIKV evolution in mice was generally more convergent and subjected to more relaxed purifying selection than that in mosquitoes or alternate passages. These findings suggest that prevention of direct human transmission chains is paramount to resist gains in ZIKV virulence. IMPORTANCE We used experimental evolution to model chains of direct and indirect Zika virus (ZIKV) transmission by serially passaging a synthetic swarm of molecularly barcoded ZIKV within and between mosquitoes and mice. We observed that direct mouse transmission chains facilitated a rapid increase in ZIKV replication and enhanced virulence in mice. These findings demonstrate that ZIKV is capable of rapid adaptation to a vertebrate host and indicate that direct human-to-human transmission poses a greater threat to public health than currently realized.en
dc.description.notesFunding for this project came from DHHS/PHS/NIH R21AI131454. The publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or NIH.en
dc.description.sponsorshipDHHS/PHS/NIH [R21AI131454]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1128/JVI.02218-20en
dc.identifier.eissn1098-5514en
dc.identifier.issn0022-538Xen
dc.identifier.issue8en
dc.identifier.othere02218-20en
dc.identifier.pmid33536175en
dc.identifier.urihttp://hdl.handle.net/10919/104458en
dc.identifier.volume95en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAedes aegyptien
dc.subjectflavivirusen
dc.subjectZika virusen
dc.subjectexperimental evolutionen
dc.subjecthost cyclingen
dc.subjectpathogenesisen
dc.subjectvirulenceen
dc.titleRapid Evolution of Enhanced Zika Virus Virulence during Direct Vertebrate Transmission Chainsen
dc.title.serialJournal of Virologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Scholarly Works, Biomedical Sciences and Pathobiology
Destination Area: Global Systems Science (GSS)