Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice

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dc.contributor.authorDuggal, Nisha K.en
dc.contributor.authorMcDonald, Erin M.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorHawks, Seth A.en
dc.contributor.authorRitter, Jana M.en
dc.contributor.authorRomo, Hannahen
dc.contributor.authorEbel, Gregory D.en
dc.contributor.authorBrault, Aaron C.en
dc.date.accessioned2019-08-29T17:12:32Zen
dc.date.available2019-08-29T17:12:32Zen
dc.date.issued2019-04en
dc.description.abstractZika virus (ZIKV) infection can result in neurological disorders including Congenital Zika Syndrome in infants exposed to the virus in utero. Pregnant women can be infected by mosquito bite as well as by sexual transmission from infected men. Herein, the variants of ZIKV within the male reproductive tract and ejaculates were assessed in inoculated mice. We identified two non-synonymous variants at positions E-V330L and NS1-W98G. These variants were also present in the passage three PRVABC59 isolate and infectious clone relative to the patient serum PRVABC59 sequence. In subsequent studies, ZIKV E-330L was less pathogenic in mice than ZIKV E-330V as evident by increased average survival times. In Vero cells, ZIKV E-330L/NS1-98G outcompeted ZIKV E-330V/NS1-98W within 3 passages. These results suggest that the E-330L/NS1-98G variants are attenuating in mice and were enriched during cell culture passaging. Cell culture propagation of ZIKV could significantly affect animal model development and vaccine efficacy studies.en
dc.description.notesThis work was supported in part by NIH grant AI067380 (G.D.E.). We thank DVBD staff members Jason Velez for cell culture support and Sean Masters for his excellent contributions to animal husbandry and animal care needs throughout this study. The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the U.S. Agency for International Development.en
dc.description.sponsorshipNIH [AI067380]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.virol.2019.02.004en
dc.identifier.issn0042-6822en
dc.identifier.pmid30763872en
dc.identifier.urihttp://hdl.handle.net/10919/93304en
dc.identifier.volume530en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectZika virusen
dc.subjectFlavivirusen
dc.subjectMouse modelen
dc.subjectViral pathogenesisen
dc.titleMutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in miceen
dc.title.serialVirologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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