Document 0214
 DOCN  M9440214
 TI    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.
 DT    9404
 AU    Popik W; Pitha PM; Oncology Center, Johns Hopkins University School of
       Medicine,; Baltimore, Maryland 21231.
 SO    J Virol. 1994 Mar;68(3):1324-33. Unique Identifier : AIDSLINE
       MED/94149819
 AB    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.
 DE    Cell Compartmentation  Cell Line  Defective Viruses/DRUG EFFECTS/*GROWTH
       & DEVELOPMENT  Gene Products, tat/*PHARMACOLOGY  Genes, rev  Genome,
       Viral  *Herpesvirus 1, Human  HIV-1/DRUG EFFECTS/*GROWTH & DEVELOPMENT
       Polyribosomes/CHEMISTRY  RNA, Messenger/ANALYSIS  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/*MICROBIOLOGY
       Transfection  Translation, Genetic  Tumor Necrosis Factor/*PHARMACOLOGY
       Viral Proteins/BIOSYNTHESIS  Virus Activation/*DRUG EFFECTS  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).