IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection
Cubillos-Ruiz, Juan R.
Vrbanac, Vladimir D.
Murooka, Thomas T.
Dudek, Timothy E.
Kwon, Douglas S.
Glimcher, Laurie H.Note: Order does not necessarily reflect citation order of authors.
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CitationAdoro, S., J. R. Cubillos-Ruiz, X. Chen, M. Deruaz, V. D. Vrbanac, M. Song, S. Park, et al. 2015. “IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection.” Nature Communications 6 (1): 7562. doi:10.1038/ncomms8562. http://dx.doi.org/10.1038/ncomms8562.
AbstractInitial 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.
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