title: Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus.
abstract: The herpes simplex virus type 1 (HSV-1)-mediated transactivation of human immunodeficiency virus type 1 (HIV-1) provirus was studied in cell lines containing either integrated tat-defective HIV-1 provirus (HNHIVdt4 cells) or the tat-defective HIV-1 provirus, and a plasmid in which the expression of human alpha 2 interferon (HuIFN-alpha 2) was under the control of the HIV-1 long terminal repeat (LTR) (HNHIV alpha 1 cells). In both cell lines, transcription of the HIV-1 provirus was below the limits of detection, but it could be induced effectively by transfection with a HIV-1 tat-expression plasmid. In HNHIV alpha 1 cells, HuIFN-alpha 2 was induced concomitantly with HIV-1 provirus, although these cells synthesized only low levels of IFN constitutively. In contrast, infections with HSV-1 activated transcription of HIV-1 provirus only in HNHIVdt4 cells but not in HNHIV alpha 1 cells. Similarly in a transient expression assay, HSV-1 up-regulated expression of a HIV LTR-CAT (chloramphenicol acetyltransferase gene) plasmid in HNHIVdt4 but not in HNHIV alpha 1 cells. No major differences could be detected in the expression of HSV-1 immediate-early (IE) genes IE175 and IE110 (which are essential for the activation of HIV-1 LTR) in HNHIVdt4 and HNHIV alpha 1 cells to account for the inability of HSV-1 to induce HIV-1 in HNHIV alpha 1 cells. However, major differences were observed in the binding pattern of NF-kappa B-specific nuclear proteins to the enhancer region of the HIV-1 LTR: whereas binding of the 45-kDa NF-kappa B-specific nuclear protein was detected in nuclear extracts from HNHIVdt4 cells, no protein binding was seen in extracts from HNHIV alpha 1 cells. These results suggest an alternate mechanism by which IFN may alter the expression of cellular and viral genes.
authors.affiliation: Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: W
authors.initials: W
authors.lastname: Popik
authors.forename: P M
authors.initials: PM
authors.lastname: Pitha
mesh_terms: D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000502:physiology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006561:Herpes Simplex / Q000382:microbiology; D006801:Humans; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D007372:Interferons / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011533:Proviruses / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics*; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D054322:tat Gene Products, Human Immunodeficiency Virus; D007372:Interferons; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1