Suppression of HIV-1 transcription by beta-chemokines RANTES, MIP1-alpha, and MIP-1beta is not mediated by the NFAT-1 enhancer element.

Soluble factors derived from human CD8+ T-lymphocytes inhibit HIV-1 replication by suppressing transcription from the viral long terminal repeat (LTR), an effect shown to be mediated in part by an NFAT-1 enhancer sequence. We show here that the CD8+ derived beta-chemokines, RANTES, MIP1-alpha, and MIP-1beta, known suppressors of HIV-1 replication in human peripheral blood mononuclear cells, can suppress transcription from the HIV-1 LTR in transient transfection assays in cells of the Jurkat (acute T leukemia) line. Surprisingly, the suppression mediated by these beta-chemokines persisted in the absence of an intact NFAT-1 element, suggesting that there are at least two classes of HIV-1 suppressor factors--NFAT-1-dependent and NFAT-1-independent factors--produced by CD8+ T-lymphocytes.