Differential regulation of the HIV-1 LTR by specific NF-kappa B subunits in HSV-1-infected cells

Previous studies have shown that expression of HIV-1 provirus was enhanced in cells co-infected with the herpes virus and that HSV-1-mediated induction of the HIV-1 provirus expression involved both NF-kappa B-dependent and NF-kappa B-independent mechanisms. Nuclear NF-kappa B complexes could be detected approximately 8 hr after HSV-1 infection. Using NF-kappa B-specific antibodies in a mobility shift assay. we have found that HSV-1 increases binding of p50, p65, and c-rel to the HIV-1 NF-kappa B probe in both Jurkat T cells and NIH/3T3 cells. HSV-1 infection also increases transiently the levels of p50 mRMA but an increase in the level of p65 mRNA was not detected. Furthermore, HSV-I infection induces a rapid degradation of the I kappa B alpha protein. Transfection of HIV-1 LTR CAT into cell lines which overexpressed individual NF-kappa B proteins showed the highest constitutive expression of CAT activity in cells overexpressing p65. infection with HSV-1 further enhanced the expression of HIV-I LTR CAT in cell lines producing p52, p100. and c-rel. In contrast HSV-1 did not significantly enhance the expression of HIV-I LTR CAT in cell lines overexpressing p105 and I kappa B gamma. In the transient expression assay the p65/c-rel heterodimer was the most effective inducer of the HIV-1 LTR expression. Thus it appears that p65 plays a limited role in the NF-kappa B-dependent activation of the HIV-1 LTR following HSV-1 infection and that the stimulation is mediated by the p50/p65 and p65/c-rel heterodimers. Thus the magnitude of HIV-1 provirus induction depends on the relative levels of NF-kappa B subunits present in the infected cells. (C) 1996 Academic Press, Inc.