Stimulatory effect of the CYPlAl inducer 2,3,7,8-tetrachlorodibenzo-pdioxin on the reproduction of HIV-1 in human lymphoid cell culture

Abstract

1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was an inducer of microsomal benzo[α;]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.