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 R. Klatt, Michael Gale and Deborah Heydenburg Fuller ()
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Megan A. O’Connor: University of Washington
Jennifer Tisoncik-Go: University of Washington
Thomas B. Lewis: University of Washington
Charlene J. Miller: University of Washington
Debra Bratt: Washington National Primate Research Center
Cassie R. Moats: Washington National Primate Research Center
Paul T. Edlefsen: Fred Hutchinson Cancer Research Center
Jeremy Smedley: Washington National Primate Research Center
Nichole R. Klatt: Washington National Primate Research Center
Michael Gale: University of Washington
Deborah Heydenburg Fuller: University of Washington

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05826-w

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