Document 0557
 DOCN  M9650557
 TI    Interferon-gamma-induced downregulation of CD4 inhibits the entry of
       human immunodeficiency virus type-1 in primary monocytes.
 DT    9605
 AU    Dhawan S; Heredia A; Wahl LM; Epstein JS; Meltzer MS; Hewlett IK;
       Laboratory of Molecular Virology, Food and Drug Administration,;
       Rockville, Md., USA.
 SO    Pathobiology. 1995;63(2):93-9. Unique Identifier : AIDSLINE MED/96108566
 AB    We have previously shown that the treatment of monocytes with
       interferon-gamma (IFN-gamma) prior to exposure with human
       immunodeficiency virus type-1 (HIV) results in complete inhibition of
       HIV infection of monocytes. In the present report, we have extended this
       study to obtain information on the mechanism(s) underlying
       IFN-gamma-induced inhibition of HIV infection of monocytes. To examine
       the effect of IFN-gamma on HIV entry, the first event in the infectious
       cycle of the virus, we amplified HIV-gag sequences in the genomic DNA
       and RNA of IFN-gamma treated monocytes, and found no evidence for the
       presence of either proviral DNA or HIV RNA sequences. These results were
       consistent with the absence of intracellular HIV particles either in the
       latent or actively replicating state as determined by flow-cytometric
       analysis of these cells. Furthermore, no HIV-induced cytopathic effects,
       such as multinucleated giant cell formation or cell death, were observed
       in IFN-gamma-treated monocytes after their exposure to HIV. Stimulation
       of IFN-gamma-treated monocytes 6 days postinfection with tumor necrosis
       factor-alpha (TNF-alpha), which is known to augment HIV replication in
       the infected cells, did not result in the induction of the HIV
       indicating the absence of latent HIV infection in IFN-gamma-treated
       monocytes. Treatment of monocytes with IFN-gamma, TNF-alpha, or with a
       combination of the two agents which is known to induce antimicrobial
       free radical nitric oxide (NO2- in the murine system did not induce NO2-
       production human monocytes suggesting the antiviral activity of
       IFN-gamma to be independent of NO2(-)-mediated killing of HIV or
       HIV-infected monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Antigens, CD4/*BIOSYNTHESIS  Cells, Cultured  Cytopathogenic Effect,
       Viral  *Down-Regulation (Physiology)  Human  HIV Core Protein
       p24/BIOSYNTHESIS  HIV-1/PHYSIOLOGY/*PATHOGENICITY  Interferon Type
       II/*PHARMACOLOGY  Kinetics  Monocytes/IMMUNOLOGY/*VIROLOGY  Nitric
       Oxide/METABOLISM  Polymerase Chain Reaction  Transfection  Tumor
       Necrosis Factor/PHARMACOLOGY  Virus Replication  JOURNAL ARTICLE

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