Interactions of retroviruses with chemical carcinogens: I. Noncovalent binding of unactivated polycyclic aromatic hydrocarbons

Abstract

The noncovalent binding of carcinogenic polycyclic aromatic hydrocarbons (PAH), e.g., benzo( a)pyrene, to retroviruses was quantitated using a rate zonal centrifugation assay, and the effects of the binding on a retrovirus specific function, reverse transcription, were determined. The level of binding for the enveloped retroviruses was much higher than that found for nonenveloped viruses (2.5 to 40-fold greater), such as bacteriophage T4 and adenovirus type 5; there was no special affinity of PAH compounds for retroviruses as compared with another enveloped virus, Sindbis virus; and there was no binding to the viral glycoproteins (type specific antigens). These results suggest that the binding is best interpreted as partitioning of the hydrophobic PAH compounds between viral envelope lipids and the surrounding aqueous buffer, and this interpretation is supported by the temperature and salt dependence of the binding. Using isolated retroviral cores we also found that there is a relatively small, but significant, level of binding of benzo( a)pyrene to retroviral cores. Further, we observed that the noncovalent binding of benzo( a)pyrene to Rauscher leukemia virus inhibits the RNA-dependent DNA polymerase activity. The inhibition requires preincubation of the virus and PAH, i.e., the formation of noncovalent virus-PAH complexes, and is consistent with a noncompetitive model of enzyme inhibition with an inhibition constant, K i of about 40 μ M.