Effect of combined alpha IFN and prostaglandin A(1) treatment on vesicular stomatitis virus replication and heat shock protein synthesis in epithelial cells

The antiviral activity of prostaglandin A (PGA) and interferons (IFNs) has been widely described. In the present report, we investigated the effect of combined alpha IFN and PGA(1) treatment on vesicular stomatitis virus (VSV) replication and on heat shock protein (HSP) induction in monkey epithelial cells. In uninfected cells, PGA(1) caused a dose-dependent induction of HSP70, HSP90 and HSP110, while alpha IFN did not affect HSP synthesis. Alpha-IFN suppressed VSV replication dose-dependently, even when cells were treated after virus infection. VSV protein synthesis was not affected by alpha IFN, indicating a block at the level of virus assembly or maturation. PGA(1) caused a dose-dependent inhibition of VSV replication, and suppressed VSV protein synthesis at concentrations which induced the synthesis of high levels of HSP70. The combined treatment with low doses of alpha IFN or PGA(1), which only moderately inhibited VSV replication when administered separately, was found to suppress VSV production by more than 95%, and resulted in a 3-fold increase of HSP70 synthesis as compared to PGA(1) alone. These results demonstrate a co-operative effect of PGA(1) and alpha IFN against VSV infection and suggest that alpha IFN can potentiate the cellular response to HSP induction in virus-infected cells.