title: TRAF6 and IRF7 control HIV replication in macrophages.
abstract: The innate immune system recognizes virus infection and evokes antiviral responses which include producing type I interferons (IFNs). The induction of IFN provides a crucial mechanism of antiviral defense by upregulating interferon-stimulated genes (ISGs) that restrict viral replication. ISGs inhibit the replication of many viruses by acting at different steps of their viral cycle. Specifically, IFN treatment prior to in vitro human immunodeficiency virus (HIV) infection stops or significantly delays HIV-1 production indicating that potent inhibitory factors are generated. We report that HIV-1 infection of primary human macrophages decreases tumor necrosis factor receptor-associated factor 6 (TRAF6) and virus-induced signaling adaptor (VISA) expression, which are both components of the IFN signaling pathway controlling viral replication. Knocking down the expression of TRAF6 in macrophages increased HIV-1 replication and augmented the expression of IRF7 but not IRF3. Suppressing VISA had no impact on viral replication. Overexpression of IRF7 resulted in enhanced viral replication while knocking down IRF7 expression in macrophages significantly reduced viral output. These findings are the first demonstration that TRAF6 can regulate HIV-1 production and furthermore that expression of IRF7 promotes HIV-1 replication.
authors.affiliation: Department of Molecular Medicine, Infectious Disease Research Center, CHUL Research Center and Laval University, Québec, Québec, Canada.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Sirois
authors.forename: Lynda
authors.initials: L
authors.lastname: Robitaille
authors.forename: Robin
authors.initials: R
authors.lastname: Allary
authors.forename: Mohak
authors.initials: M
authors.lastname: Shah
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Woelk
authors.forename: Jérôme
authors.initials: J
authors.lastname: Estaquier
authors.forename: Jacques
authors.initials: J
authors.lastname: Corbeil
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D056726:Genetic Association Studies; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000821:virology*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; C505371:MAVS protein, human; D048029:TNF Receptor-Associated Factor 6