HUMAN TRANSCRIPTION FACTOR YY1 REPRESSES HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 TRANSCRIPTION AND VIRION PRODUCTION

The transcriptional activity of human immunodeficiency virus type 1 (H IV-1) is affected by many cellular factors. Homologies near the HIV-I initiator region to the DNA-binding sequences of YY1, a multifunctiona l transcription factor known to regulate diverse viral and cellular pr omoters, suggested that YY1 might regulate HIV-1. Antibody to YY1 bloc ked the formation of complexes by HeLa cell nuclear extract and a DNA oligonucleotide encoding the HIV-1 initiator region. HIV-1 long termin al repeat (LTR) expression, as measured the expression of a transfecte d LTR-CAT reporter gene, was repressed more than 12-fold by the cotran sfection of a YY1 expression vector. HIV-I production by both COS-1 an d CEM cells after transfection of an infectious molecular HIV-1 clone was repressed 7- to 20-fold by cotransfection of a YY1 expression vect or. HIV-1 production was also decreased threefold in a CD4-positive ly mphocyte cell line chronically infected with HIV-1 (8E5) after transfe ction of YY1. In situ hybridization studies confirmed that YY1 reduced HIV-1 RNA expression. YY1 may play an important role in the regulatio n of HIV-1 LTR expression in vivo and virus production by infected cel ls.