title: MCPIP1/regnase-I inhibits simian immunodeficiency virus and is not counteracted by Vpx.
abstract: We have previously shown that the cellular RNase MCPIP1/regnase-1 potently blocks HIV-1 infection in resting CD4+ T-cells. As simian immunodeficiency virus (SIV) encodes an accessory protein named Vpx, which enhances viral replication in resting CD4+ T-cells by degrading the cellular restriction factor SAMHD1, we investigated whether MCPIP1 restricts SIV infection and whether Vpx protein antagonizes MCPIP1-mediated restriction. In co-transfection studies, human MCPIP1 markedly reduced the production of infectious SIV, whereas MCPIP2 and MCPIP3 had little effect. MCPIP1 derived from cynomolgus monkey also inhibited human immunodeficiency virus (HIV-1) and SIV production, albeit to a lesser degree. Lastly, expression of SIV Vpx protein did not reduce MCPIP1 at the protein level, nor did it ablate the MCPIP1-mediated restriction. In conclusion, both human and cynomolgus monkey MCPIP1 restrict SIV replication. Unlike SAMHD1, MCPIP1-mediated HIV-1 restriction cannot be overcome by SIV Vpx.
authors.affiliation: Research Institute of Medicine and Pharmacy, Qiqihar Medical University, 333 Bukui North Street, Heilongjiang 161006, PR China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Infectious Diseases, Bioscience Division, SRI International, 140 Research Drive, Harrisonburg, VA 22802, USA.
authors.forename: Tony T
authors.initials: TT
authors.lastname: Wang
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D008252:Macaca fascicularis; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D000076106:SAM Domain and HD Domain-Containing Protein 1; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D014157:Transcription Factors; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D012260:Ribonucleases; C510646:ZC3H12A protein, human; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D020559:Monomeric GTP-Binding Proteins