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 differen t human immunodeficiency virus type 1 (HIV-I) promoter and/or transact ivator activities. We therefore analyzed the sequences and activities of the first exon of Tat, tat1, and the prometer/trans-acting responsi ve (TAR) regions amplified directly from peripheral blood mononuclear cells obtained from five long-term nonprogressors and eight progressin g HIV-1-infected individuals. The majority of tat1 alleles and promote r/TAR regions from all patients were intact and showed comparable acti vities in transient reporter assays, A substantial number of point mut ations and some length variations were observed in the promoter/TAR re gion. In a single nonprogressor, the Spl binding site 3 was consistent ly altered and the transcriptional activity in the presence of Tat was diminished. Some LTR clones from a rapid progressor contained a fourt h Spl binding site, which was associated with an elevated basal promot er activity. These data suggest that defects in the promoter/TAR regio n or tat1 are rare and that different promoter/transactivator activiti es are not commonly associated with different progression rates. (C) 1 997 Academic Press.