title: MCPIP1 restricts HIV infection and is rapidly degraded in activated CD4+ T cells.
abstract: HIV-1 primarily infects activated CD4+ T cells and macrophages. Quiescent CD4+ T cells, however, possess cellular factors that limit HIV-1 infection at different postentry steps of the viral life cycle. Here, we show that the previously reported immune regulator monocyte chemotactic protein-induced protein 1 (MCPIP1) restricts HIV-1 production in CD4+ T cells. While the ectopic expression of MCPIP1 in cell lines abolished the production of HIV-1, silencing of MCPIP1 enhanced HIV-1 production. Subsequent analysis indicated that MCPIP1 imposes its restriction by decreasing the steady levels of viral mRNA species through its RNase domain. Remarkably, common T-cell stimuli induced the rapid degradation of MCPIP1 in both T-cell lines and quiescent human CD4+ T cells. Lastly, blocking the proteosomal degradation of MCPIP1 by MG132 abrogated HIV-1 production in phorbol 12-myristate 13-acetate/ionomycin-stimulated human CD4+ T cells isolated from healthy donors. Overall, MCPIP1 poses a potent barrier against HIV-1 infection at a posttranscriptional stage. Although the observed HIV restriction conferred by MCPIP1 does not seem to be overcome by any viral protein, it is removed during cellular stimulation. These findings provide insights into the mechanisms of cellular activation-mediated HIV-1 production in CD4+ T cells.
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA 15261.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Qiu
authors.forename: Ruidong
authors.initials: R
authors.lastname: Miao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Aram
authors.initials: A
authors.lastname: Lee
authors.forename: Baoming
authors.initials: B
authors.lastname: Liu
authors.forename: Sandra N
authors.initials: SN
authors.lastname: Lester
authors.forename: Weihui
authors.initials: W
authors.lastname: Fu
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhu
authors.forename: Linxia
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.forename: Mingui
authors.initials: M
authors.lastname: Fu
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wang
mesh_terms: D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D057809:HEK293 Cells; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D015151:Immunoblotting; D007976:Leupeptins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D007976:Leupeptins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: antiviral immunity; restriction factor