Inhibition of Herpesvirus saimiri replication by phosphonoacetic acid, benzo(a)pyrene, and methylcholanthrene

The present investigations were undertaken to determine the possible effects of two carcinogenic polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene on Herpesvirus saimiri replication. The results from these experiments were compared with the effects of phosphonoacetic acid on the virus replication cycle. Phosphonoacetic acid inhibited the synthesis of virus-induced intracellular late antigens, membrane antigens and infectious virus but not the synthesis of the early antigens induced by H. saimiri. In contrast, benzo(a)pyrene and 3-methylcholanthrene inhibited primarily membrane antigen expression and infectious virus production. Benzo(a)pyrene was the most effective of the two compounds, with significant inhibition occurring with 2 mug/ml, whereas a minimum concentration of 10 mug/ml was required with 3-methylcholanthrene. Both compounds were most effective when present continuously during the 4-day infection process. However, exposure of infected cultures to a 3-hr pulse with each chemical also inhibited membrane antigen expression. Furthermore, pretreatment of cells for 48 hr before virus infection resulted in the inhibition of membrane antigen expression but not that of early or late antigens. These result demonstrate that some carcinogenic chemicals are capable of altering the H. saimiri replication cycle, primarily by inhibiting some but not all late events.