title: Differential regulation of the HIV-1 LTR by specific NF-kappa B subunits in HSV-1-infected cells.
abstract: 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 mRNA but an increase in the level of p65 mRNA was not detected. Furthermore, HSV-1 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-1 LTR CAT in cell lines producing p52, p100, and c-rel. In contrast, HSV-1 did not significantly enhance the expression of HIV-1 LTR CAT in cell lines overexpressing p105 and 1 kappa B gamma. In the transient expression assay the p65/c-rel heterodimer was the most effective inducer of the HIV-I 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.
authors.affiliation: Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Schafer
authors.forename: J
authors.initials: J
authors.lastname: Hiscott
authors.forename: P M
authors.initials: PM
authors.lastname: Pitha
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins; D019169:Jurkat Cells; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D051996:Transcription Factor RelA
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha