Conditional regulatory elements of human immunodeficiency virus type 2 long terminal repeat.
Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) long terminal repeat (LTR) revealed a novel cis-acting positive and a negative regulatory element in the U3 region, located upstream of the enhancer-promoter region. These elements acted in a cell type-specific manner, being most active in human lymphocytic CEM cells, more active in Jurkat cells than in human monocytic U937 cells and least active in epithelioid HeLa cells. The down-modulatory effect of the negative regulatory element was abolished by HIV-2 Tat, suggesting the involvement of upstream DNA elements in optimal Tat-mediated trans-activation. The sequence elements that respond to T cell activation signals were also located in the upstream U3 region. Notably, the magnitude of the effect of the upstream regulatory elements depended on the basal activity of the LTR, which was also cell type-dependent. This emphasizes the importance of the cell-specific transcriptional factors and other effectors in regulating HIV gene expression. These observations may be relevant to the cell type-specific restriction of virus replication in vivo.
Arya
S K
SK
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Mohr
J R
JR
D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D016325:HIV Long Terminal Repeat; D015498:HIV-2 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection
D004279:DNA, Viral; D015500:Chloramphenicol O-Acetyltransferase