DOMINANT INHIBITORS OF TAT-INDEPENDENT HIV EXPRESSION AND VIRUS REPLICATION

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We have initiated a project to evaluate the potential of inhibitors of ETS-dependent and NFkB-dependent transcription to block the initiation of human immunodeficiency virus (HIV) infection. Prior to the expression of HIV-encoded Tat, expression of HIV long terminal repeat (LTR) regulated genes are dependent on cellular transcription factors such as NFkB and ETS. ERF encodes a protein which has been shown to be capable of inhibiting HIV LTR-dependent expression in transient assays, and linkage of the inhibitory domain of ERF to the DNA-binding domain of NFkB inhibits NFkB-dependent expression in similar assays. We generated HIV susceptible HeLa-T4 and CEMs cells expressing the ERF and the NFkB-ERF fusion proteins, respectively. Currently, we are testing the ability of these cells to support infection and replication of HIV in comparison to parental cells which do not express the inhibitory constructs.