Activity of human immunodeficiency virus type 1 promoter TAR regions and tat1 genes derived from individuals with different rates of disease progression

Different rates of disease progression may be associated with different human immunodeficiency virus type 1 (HIV-I) promoter and/or transactivator activities. We therefore analyzed the sequences and activities of the first exon of Tat, tat1, and the prometer/trans-acting responsive (TAR) regions amplified directly from peripheral blood mononuclear cells obtained from five long-term nonprogressors and eight progressing HIV-1-infected individuals. The majority of tat1 alleles and promoter/TAR regions from all patients were intact and showed comparable activities in transient reporter assays, A substantial number of point mutations and some length variations were observed in the promoter/TAR region. In a single nonprogressor, the Spl binding site 3 was consistently altered and the transcriptional activity in the presence of Tat was diminished. Some LTR clones from a rapid progressor contained a fourth Spl binding site, which was associated with an elevated basal promoter activity. These data suggest that defects in the promoter/TAR region or tat1 are rare and that different promoter/transactivator activities are not commonly associated with different progression rates. (C) 1997 Academic Press.