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Nat Commun. 2015 Jun 25;6:7562. doi: 10.1038/ncomms8562.

IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection.

Author information

1
Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
2
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
3
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
4
Institute for Medical Biology, University Hospital Essen, University of Duisburg-Essen, Essen D-45147, Germany.
5
Howard Hughes Medical Institute, Chevy Chase, Maryland 20814, USA.
6
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.

Abstract

Initial events after exposure determine HIV-1 disease progression, underscoring a critical need to understand host mechanisms that interfere with initial viral replication. Although associated with chronic HIV-1 control, it is not known whether interleukin-21 (IL-21) contributes to early HIV-1 immunity. Here we take advantage of tractable primary human lymphoid organ aggregate cultures to show that IL-21 directly suppresses HIV-1 replication, and identify microRNA-29 (miR-29) as an antiviral factor induced by IL-21 in CD4 T cells. IL-21 promotes transcription of all miR-29 species through STAT3, whose binding to putative regulatory regions within the MIR29 gene is enriched by IL-21 signalling. Notably, exogenous IL-21 limits early HIV-1 infection in humanized mice, and lower viremia in vivo is associated with higher miR-29 expression. Together, these findings reveal a novel antiviral IL-21-miR-29 axis that promotes CD4 T-cell-intrinsic resistance to HIV-1 infection, and suggest a role for IL-21 in initial HIV-1 control in vivo.

PMID:
26108174
PMCID:
PMC4481879
DOI:
10.1038/ncomms8562
[Indexed for MEDLINE]
Free PMC Article

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