Stimulatory effect of the CYP1A1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin on the reproduction of HIV-1 in human lymphoid cell culture.
1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was an inducer of microsomal benzo[alpha]pyrene hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD) in MT-4 human lymphoid cell culture. 2. The monoclonal antibody (Mab), 1-7-1 and the immunodepleted polyclonal antibody (Pab), anti-CYP1A1(-A2), inhibit AHH and EROD activities pre-induced by 10 nM TCDD in MT-4 cells. Hence, the specific monooxygenase isoform induced in the lymphoid cells by TCDD appears to be CYP1A1 the expression of which is mediated by the Ah receptor. 3. Incubation of MT-4 cells with TCDD at 10, 50 and 150 nM for 1.5 and 48 h followed by infection of the cells with human immunodeficiency virus 1 (HIV-1) was accompanied by a 3-6-fold increase in the activity of viral RNA-dependent DNA-polymerase. The most marked effect on reverse transcriptase activity occurred with 10 nM TCDD 5-9 days after HIV-1 infection. 4. In the same period there was accumulation of viral protein, determined by ELISA, with a 4-8-fold increase in production of viral protein. The above effects of TCDD have been observed even when MT-4 cells were washed 1.5 h after beginning the incubation with TCDD.
Tsyrlov
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IB
Institute of Molecular Pathology, Russian Academy of Medical Sciences, Novosibirsk.
Pokrovsky
A
A
D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D001579:Benzopyrene Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase