Effects of HIV-1 Tat on Expression of HLA Class I Molecules

Abstract

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.