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, Deborah Heydenburg Fuller

Research output: Contribution to journalArticlepeer-review

32 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
Externally publishedYes

Bibliographical note

Funding Information:
We thank all members of the Fuller laboratory for their technical support and helpful discussion. We thank B. Agricola, S. Wangari, D. May, J. Ahrens, N. Iwayama, and J. Lane for their expert support in animal husbandry and care. We also thank T. Hensley-McBain and J. Manuzak for technical support in developing the flow cytometry panels. This work was supported in part by funds from the National Institute of Health (P51-OD010425) and in part by start-up funds from WaNPRC and UW to N.R.K. M.A.O. is supported by T32-AI007140.

Publisher Copyright:
© 2018, The Author(s).

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