Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques

Megan A. O’Connor, Jennifer Tisoncik-Go, Thomas B. Lewis, Charlene J. Miller, Debra Bratt, Cassie R. Moats, Paul T. Edlefsen, Jeremy Smedley, Nichole Klatt, Michael Gale, Deborah Heydenburg Fuller

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The immunological and virological events that contribute to the establishment of Zika virus (ZIKV) infection in humans are unclear. Here, we show that robust cellular innate immune responses arising early in the blood and tissues in response to ZIKV infection are significantly stronger in males and correlate with increased viral persistence. In particular, early peripheral blood recruitment of plasmacytoid dendritic cells and higher production of monocyte chemoattractant protein (MCP-1) correspond with greater viral persistence and tissue dissemination. We also identify non-classical monocytes as primary in vivo targets of ZIKV infection in the blood and peripheral lymph node. These results demonstrate the potential differences in ZIKV pathogenesis between males and females and a key role for early cellular innate immune responses in the blood in viral dissemination and ZIKV pathogenesis.

Original languageEnglish (US)
Article number3371
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    O’Connor, M. A., Tisoncik-Go, J., Lewis, T. B., Miller, C. J., Bratt, D., Moats, C. R., Edlefsen, P. T., Smedley, J., Klatt, N., Gale, M., & Fuller, D. H. (2018). Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques. Nature Communications, 9(1), [3371]. https://doi.org/10.1038/s41467-018-05826-w