title: IL-21 induces antiviral microRNA-29 in CD4 T cells to limit HIV-1 infection.
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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.|Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Adoro
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.|Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Cubillos-Ruiz
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Maud
authors.initials: M
authors.lastname: Deruaz
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.|Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Vladimir D
authors.initials: VD
authors.lastname: Vrbanac
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.
authors.forename: Suna
authors.initials: S
authors.lastname: Park
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Murooka
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Dudek
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.|Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.affiliation: Institute for Medical Biology, University Hospital Essen, University of Duisburg-Essen, Essen D-45147, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Bowman
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.|Howard Hughes Medical Institute, Chevy Chase, Maryland 20814, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kwon
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Vanja
authors.initials: V
authors.lastname: Lazarevic
authors.affiliation: Department of Medicine, Weill Cornell Medical College, Cornell University, 1300 York Avenue, New York, New York 10065, USA.|Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000821:virology*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D046509:Tissue Culture Techniques; D000098546:Interleukin-21
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007378:Interleukins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D000098546:Interleukin-21