title: The presence of tat protein or tumor necrosis factor alpha is critical for herpes simplex virus type 1-induced expression of human immunodeficiency virus type 1.
abstract: Tat-independent transcription of human immunodeficiency virus type 1 (HIV-1) plays an important role in virus life cycle before biologically significant levels of Tat protein have been accumulated. Using a latently infected T-cell line containing an integrated Tat-defective HIV-1 provirus, we examined whether factors known to up-regulate the HIV-1 expression in vitro can replace the requirement for a functional Tat protein and induce the expression of the Tat-defective HIV-1 provirus. Both tumor necrosis factor alpha (TNF-alpha) and herpes simplex virus type 1 (HSV-1) infection stimulated transcription of the Tat-defective HIV-1 provirus to comparable levels, but in HSV-1-infected cells, the cytoplasmic HIV-1 transcripts were not efficiently translated in the absence of Tat protein and were excluded from the large polysomes. However, HSV-1 infection did not affect the distribution of cellular gamma-actin RNA or 28S RNA in the polysomal fractions. The translational block of HIV-1 RNA was not mediated by the virion-associated host cell shutoff protein (vhs); dissociation of HIV-1 transcripts from the polysomes and inefficient translation was also observed in cells infected with the vhs-defective mutant of HSV-1 (vhs-1). Overexpression of Rev protein did not rescue the synthesis of HIV-1 proteins in these cells; however, the observed inhibition of HIV-1 RNA translation was efficiently overcome in the presence of Tat protein or TNF-alpha. These findings suggest that, in contrast to TNF-alpha, HSV-1 infection is not able to induce a full cycle of HIV-1 replication and that cytokines and Tat have a critical role in the activation of HIV-1 provirus by HSV-1.
authors.affiliation: Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
authors.forename: W
authors.initials: W
authors.lastname: Popik
authors.forename: P M
authors.initials: PM
authors.lastname: Pitha
mesh_terms: D002451:Cell Compartmentation; D002460:Cell Line; D003673:Defective Viruses / Q000187:drug effects / Q000254:growth & development*; D015696:Gene Products, tat / Q000494:pharmacology*; D015757:Genes, rev; D016679:Genome, Viral; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D018259:Herpesvirus 1, Human; D011132:Polyribosomes / Q000737:chemistry; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000382:microbiology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014764:Viral Proteins / Q000096:biosynthesis; D014775:Virus Activation / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus