Effects of HIV-1 Tat on expression of HLA class I molecules.
Tat protein of HIV-1 is a potent transactivator of transcription and essential for HIV-1 replication. In addition, Tat has been proposed to possess immunosuppressive functions, suggesting that Tat may play a direct role in the immune dysfunction associated with AIDS. Recently, it has been reported that Tat represses activity of a major histocompatibility complex (MHC) class I gene promoter. Because HIV infection downmodulates expression of class I molecules, this data strongly suggests that Tat downregulates class I expression and leads to loss of CTL activity. Here, we report effects of Tat on class I expression using a human cell line, T0, expressing Tat (TO-Tat). Northern blot analysis shows that levels of MHC class I transcripts are normal in T0-Tat. Flow cytometry analyses indicate that expression of HLA class I molecules is not substantially downregulated to any great extent by Tat in T0-Tat. Further, pulse-chase experiments followed by Endoglycosidase-H treatment show that the rate of maturation and processing of class I molecules in T0-Tat is indistinguishable from that in the original cell line, T0. Taken together, these data suggest that Tat expression does not necessarily result in downregulation of class I expression.
Matsui
M
M
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, 27599-7290, USA.
Warburton
R J
RJ
Cogswell
P C
PC
Baldwin
A S
AS
Frelinger
J A
JA
D000595:Amino Acid Sequence; D001483:Base Sequence; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000096:biosynthesis* / Q000235:genetics; D005805:Genes, MHC Class I; D015497:HIV-1; D015234:HLA-A Antigens / Q000096:biosynthesis*; D006801:Humans; D007108:Immune Tolerance; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000096:biosynthesis; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015234:HLA-A Antigens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus