Document 3216
 DOCN  M94A3216
 TI    Activating effects of dioxin on HIV-1 in human CD4+ lymphoid cells.
 DT    9412
 AU    Tsyrlov IB; Pokrovsky AG; NCI/NIH, Bethesda, MD 20892.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):127 (abstract no. PA0126). Unique
       Identifier : AIDSLINE ICA10/94369359
 AB    2,3,7,8-TCDD (dioxin) and dioxin-like compounds are widely known because
       of their potential toxicity, including immunological disturbance the
       mechanism of which is still unknown. Here, effects of dioxin were
       assessed in regard to a marker enzyme CYP1A1 and HIV-1 genes. Dioxin and
       HIV-1 both affect the same target cells, i.e. human CD4+ lymphocytes.
       Induction with 1.0 nM dioxin of CYP1A1 activity was demonstrated. It was
       also shown that 1.0 nM dioxin was a potent activator of HIV-1 reverse
       transcriptase in CD4+ cells, i.e. there was 3- to 6-fold increase of
       enzyme activity. As for viral protein, its content estimated by ELISA in
       dioxin-treated CD4+ cells was 4-8-fold greater than in control group. In
       this study we found also that several polycyclic hydrocarbons stimulated
       in CD4+ cells the CYP1A1 activity and HIV-1 production. The decisive
       problem of AIDS desease is what are the factors responsible for
       transformation of HIV-positive patients to clinical manifestation, and
       the mechanisms participating in this transformation. The results
       obtained here indicate that even 1.0 nM dioxin had a marked stimulatory
       effect on HIV-1 production in primary HIV-infected CD4+ cells. As the
       same concentration of dioxin caused the Ah receptor-mediated induction
       of CYP1A1, it allowed to suggest that intracellular receptor-ligand
       complex is also involved in trans-activation of HIV-1 gene. In most
       cases known, a trans-activation of the HIV-1 gene is a decisive step in
       the regulation of its reproduction. The Ah receptor is a regulatory
       protein participating in trans-activation of Cyp1a1 gene expression.
       Although requiring experimental verification, a suggestion seems logical
       on a similar mechanism involved in activation of HIV-1 gene by dioxin.
       If this is the case, an effective competitor with dioxin (or
       benzo[a]pyrene in tabacco smoke) for the Ah-receptor could be checked.
       Using the model described, we have tested some natural flavonoids, which
       are shown to compete with dioxin for the Ah-receptor, as potential
       anti-HIV drugs.
 DE    Comparative Study  Cytochrome P-450/BIOSYNTHESIS  Dioxins/*PHARMACOLOGY
       Enzyme Activation  Enzyme-Linked Immunosorbent Assay  Gene Expression
       Regulation, Viral/DRUG EFFECTS  Genes, Viral  Human  HIV-1/DRUG
       EFFECTS/*GROWTH & DEVELOPMENT/METABOLISM  Reverse
       Transcriptase/METABOLISM  Trans-Activation (Genetics)  T4
       Lymphocytes/*MICROBIOLOGY/PHYSIOLOGY  Viral
       Proteins/ANALYSIS/BIOSYNTHESIS  Virus Activation/*DRUG EFFECTS  MEETING
       ABSTRACT

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