HIV Tat represses transcription of the beta 2-microglobulin promoter.
The MHC class I complex, which binds and presents peptide antigen, is composed of a class I heavy chain and the beta2-microglobulin light chain. HIV-1, which induces a profound immunodeficiency in infected individuals, encodes proteins that cause decreased expression of class I heavy chain. We now report that the HIV Tat protein, which is a potent transactivator of viral transcription, is also a potent repressor of the beta2-microglobulin gene. Repression is mediated through the basal promoter of the beta2-microglobulin gene, which is shown to be predominantly regulated by an initiator element. Tat repression is further augmented by the short viral transcript, TAR, which interacts with Tat. Tat-mediated repression of beta2-microglobulin expression, together with its known repression of class I gene transcription, provides an effective mechanism by which HIV could prevent cell surface expression of the MHC class I complex and avoid immune surveillance.
Carroll
I R
IR
Molecular Regulation Section, Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Wang
J
J
Howcroft
T K
TK
Singer
D S
DS
D000818:Animals; D001483:Base Sequence; D015696:Gene Products, tat / Q000502:physiology*; D016325:HIV Long Terminal Repeat / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology*; D012097:Repressor Proteins / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000037:antagonists & inhibitors / Q000235:genetics*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D012097:Repressor Proteins; D001613:beta 2-Microglobulin; D054322:tat Gene Products, Human Immunodeficiency Virus