02287nas a2200349   4500000000100000008004100001653001400042653003000056653001500086653001500101653003900116100001300155700001000168700001600178700001500194700001500209700001300224700001000237700001300247700002000260700001200280700001300292700001600305700001300321700001400334245014800348856009900496300001300595490000700608520130800615022001401923       2018                            d10aVenezuela10aImmunologic investigation10aAcute Zika10aZika virus10aNeglected tropical diseases (NTDs)1 aCarlin A1 aWen J1 aVizcarra EA1 aMcCauley M1 aChaillon A1 aAkrami K1 aKim C1 aNgono AE1 aLara-Marquez ML1 aSmith D1 aGlass CK1 aSchooley RT1 aBenner C1 aShresta S00aA longitudinal systems immunologic investigation of acute Zika virus infection in an individual infected while traveling to Caracas, Venezuela.  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0007053&type=printable  ae00070530 v123 a<p>Zika virus (ZIKV) is an emerging mosquito-borne flavivirus linked to devastating neurologic diseases. Immune responses to flaviviruses may be pathogenic or protective. Our understanding of human immune responses to ZIKV in vivo remains limited. Therefore, we performed a longitudinal molecular and phenotypic characterization of innate and adaptive immune responses during an acute ZIKV infection. We found that innate immune transcriptional and genomic responses were both cell type- and time-dependent. While interferon stimulated gene induction was common to all innate immune cells, the upregulation of important inflammatory cytokine genes was primarily limited to monocyte subsets. Additionally, genomic analysis revealed substantial chromatin remodeling at sites containing cell-type specific transcription factor binding motifs that may explain the observed changes in gene expression. In this dengue virus-experienced individual, adaptive immune responses were rapidly mobilized with T cell transcriptional activity and ZIKV neutralizing antibody responses peaking 6 days after the onset of symptoms. Collectively this study characterizes the development and resolution of an in vivo human immune response to acute ZIKV infection in an individual with pre-existing flavivirus immunity.</p>
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