title: Regulation of class II expression in monocytic cells after HIV-1 infection.
abstract: Human macrophage hybridoma cells were used to study HLA-DR expression after HIV-1 infection. HLA-DR surface expression was lost 2 wk after infection that was associated with decreased mRNA transcription. Transfecting HLA-DR-alpha and HLA-DR-beta cDNA driven by a nonphysiological CMV promoter restored expression, suggesting that regulatory DNA-binding proteins may be affected by HIV-1 infection. There was no protein binding to conserved class II DNA elements (W/Z/S box, X-1 and X-2 boxes, and Y box) in a HIV-1-infected human macrophage hybridoma cell line, 43(HIV), and in primary monocytes that lost HLA-DR expression after HIV-1(BaL) infection. PCR analysis of the HIV-1-infected cells that lost HLA-DR expression revealed mRNA for W/Z/S (RFX-5), X-1 (RFX-5), X-2 (hX-2BP), and one Y box DNA-binding protein (NF-YB), and CIITA, a non-DNA-binding protein necessary for class II transcription. There was no mRNA for the Y box-binding protein, NF-YA. However, HLA-DR expression could be restored by transfection with NF-YA driven by a CMV promoter, although HLA-DR failed to localize in either the late endosomes, lysosomes, or acidic compartments. This was associated with a loss of class II-associated invariant chain peptide and leupeptin-induced protein in the 43(HIV) cells. To address this further, non-HIV-1-infected 43 cells were infected with vaccinia virus containing HIV-1 gag, nef, pol, and env proteins. HLA-DR failed to localize in neither the late endosomes, lysosomes, or acidic compartments in the vaccinia-infected cells containing HIV-1 env protein. HIV-1 appears to have multiple effects on class II expression in monocytic cells that may contribute to the immune defects seen in HIV-1-infected patients.
authors.affiliation: Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rakoff-Nahoum
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Kraus
authors.forename: I
authors.initials: I
authors.lastname: George
authors.forename: E
authors.initials: E
authors.lastname: Oei
authors.forename: M
authors.initials: M
authors.lastname: Tyorkin
authors.forename: E
authors.initials: E
authors.lastname: Salik
authors.forename: P
authors.initials: P
authors.lastname: Beuria
authors.forename: K
authors.initials: K
authors.lastname: Sperber
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002451:Cell Compartmentation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D005802:Genes, MHC Class II; D015488:HIV Antigens / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics; D006684:HLA-DR Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006825:Hybridomas; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000502:physiology; D051840:Y-Box-Binding Protein 1
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015488:HIV Antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C045084:invariant chain