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Nat Commun. 2018 Aug 22;9(1):3371. doi: 10.1038/s41467-018-05826-w.

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

Author information

1
Department of Microbiology, University of Washington, Seattle, 98195, WA, USA.
2
Washington National Primate Research Center, Seattle, 98121, WA, USA.
3
Department of Immunology, University of Washington, Seattle, 98109, WA, USA.
4
Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, 98109, WA, USA.
5
Department of Pharmaceutics, University of Washington, Seattle, 98195, WA, USA.
6
Department of Pediatrics, University of Miami, Miami, 33136, FL, USA.
7
Oregon National Primate Research Center, Hillsboro, 97006, OR, USA.
8
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA.
9
Department of Microbiology, University of Washington, Seattle, 98195, WA, USA. fullerdh@wanprc.org.
10
Washington National Primate Research Center, Seattle, 98121, WA, USA. fullerdh@wanprc.org.

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.

PMID:
30135445
PMCID:
PMC6105614
DOI:
10.1038/s41467-018-05826-w
[Indexed for MEDLINE]
Free PMC Article

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