INTERACTIONS BETWEEN THE HUMAN IMMUNODEFICIENCY VIRUS AND HERPESVIRUSES

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We have been studying the interactions between HSV and HIV genes at a molecular level. In the first project we are examining the mechanism by which HSV-1 activates HIV RNA transcription. The bulk of HSV activation is dependant on the integrity of Sp1 and NF-kB enhancers in the HIV LTR. HSV also activates the LTR by inducing the expression of a cellular protein that binds near the HIV transcriptional start site. Competition experiments proved the binding specificity of the protein and uV-cross linking studies identified a novel 45kD protein. We are currently attempting to purify the protein, termed LBP-2. In the second series of studies we showed that the HIV tat transactivates the HSV-1 latency-associated gene. Transient expression assays showed marked upregulation of LAT promoter but not other classes of HSV-1 promoters. Site-directed alterations in the LAT promoter sequence are being used to define that tat target.