Document 0148
 DOCN  M9460148
 TI    HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary
       human macrophages independent of productive infection.
 DT    9404
 AU    Herbein G; Keshav S; Collin M; Montaner LJ; Gordon S; Sir William Dunn
       School of Pathology, University of Oxford, UK.
 SO    Clin Exp Immunol. 1994 Mar;95(3):442-9. Unique Identifier : AIDSLINE
       MED/94185313
 AB    Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta
       may play a role in immunopathogenesis of AIDS. We studied early effects
       (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of
       HIV-1 on TNF-alpha and IL-1 beta mRNA expression in primary human
       macrophages by a semi-quantitative reverse transcriptase-polymerase
       chain reaction (RT-PCR) assay. Three-day-old monocyte-derived
       macrophages were exposed either to tissue culture supernatants
       containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to
       control supernatants free of virions and gp120. ADA strain, but not
       IIIB, replicated in primary tissue culture-differentiated macrophages
       (TCDM). Soluble CD4 (sCD4) was used to inhibit binding of both strains
       to macrophages. We found that TNF-alpha and IL-1 beta gene expression
       was induced by both strains 0.5-3 h after addition of virus, and that
       enhanced expression of both cytokines was inhibited by sCD4. We conclude
       that CD4-dependent binding to the cell surface is sufficient to enhance
       TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in
       primary human macrophages is not required. Therefore, similar pathways
       regulate gene expression of TNF-alpha and IL-1 beta by macrophages
       during initial infection by HIV-1 in vitro.
 DE    Antigens, CD4/PHARMACOLOGY  Base Sequence  Comparative Study  Gene
       Expression Regulation  Human  HIV Infections/*METABOLISM  *HIV-1
       Interleukin-1/*BIOSYNTHESIS  Macrophages/DRUG EFFECTS/*METABOLISM
       Molecular Sequence Data  Polymerase Chain Reaction  Reverse
       Transcriptase  RNA, Messenger/ANALYSIS  Support, Non-U.S. Gov't  Tumor
       Necrosis Factor/*BIOSYNTHESIS  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).