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-1) promoter and/or transactivator activities. We therefore analyzed the sequences and activities of the first exon of Tat, tat1, and the promoter/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 Sp1 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 Sp1 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.
Kirchhoff
F
F
Institute for Clinical and Molecular Virology, Friedrich-Alexander University, Erlangen, Germany. fkkirchh@viro.med.uni-erlangen.de
Greenough
T C
TC
Hamacher
M
M
Sullivan
J L
JL
Desrosiers
R C
RC
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D004279:DNA, Viral; D018450:Disease Progression; D015756:Genes, tat; D015658:HIV Infections / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015533:Transcriptional Activation
D004279:DNA, Viral