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-specifi c manner, being most active in human lymphocytic CEM cells, more activ e 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 involvem ent 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 activ ity of the LTR, which was also cell type-dependent. This emphasizes th e importance of the cell-specific transcriptional factors and other ef fecters in regulating HIV gene expression. These observations may be r elevant to the cell type-specific restriction of virus replication in vivo.