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Nat Microbiol. 2017 Nov;2(11):1462-1470. doi: 10.1038/s41564-017-0035-0. Epub 2017 Oct 2.

CD14+CD16+ monocytes are the main target of Zika virus infection in peripheral blood mononuclear cells in a paediatric study in Nicaragua.

Author information

1
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, 94720-3370, CA, USA.
2
Universidad de San Francisco de Quito, Quito, 170157, Ecuador.
3
Sustainable Sciences Institute, Managua, 14007, Nicaragua.
4
Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, 16064, Nicaragua.
5
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, 94720-3370, CA, USA. eharris@berkeley.edu.

Abstract

The recent Zika pandemic in the Americas is linked to congenital birth defects and Guillain-Barré syndrome. White blood cells (WBCs) play an important role in host immune responses early in arboviral infection. Infected WBCs can also function as 'Trojan horses' and carry viruses into immune-sheltered spaces, including the placenta, testes and brain. Therefore, defining which WBCs are permissive to Zika virus (ZIKV) is critical. Here, we analyse ZIKV infectivity of peripheral blood mononuclear cells (PBMCs) in vitro and from Nicaraguan Zika patients and show CD14+CD16+ monocytes are the main target of infection, with ZIKV replication detected in some dendritic cells. The frequency of CD14+ monocytes was significantly decreased, while the CD14+CD16+ monocyte population was significantly expanded during ZIKV infection compared to uninfected controls. Viral RNA was detected in PBMCs from all patients, but in serum from only a subset, suggesting PBMCs may be a reservoir for ZIKV. In Zika patients, the frequency of infected cells was lower but the percentage of infected CD14+CD16+ monocytes was significantly higher compared to dengue cases. The gene expression profile in monocytes isolated from ZIKV- and dengue virus-infected patients was comparable, except for significant differences in interferon-γ, CXCL12, XCL1, interleukin-6 and interleukin-10 levels. Thus, our study provides a detailed picture of the innate immune profile of ZIKV infection and highlights the important role of monocytes, and CD14+CD16+ monocytes in particular.

PMID:
28970482
PMCID:
PMC5997390
DOI:
10.1038/s41564-017-0035-0
[Indexed for MEDLINE]
Free PMC Article

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