INHIBITION OF POLIOVIRUS REPLICATION BY PROSTAGLANDIN-A AND PROSTAGLANDIN-J HUMAN-CELLS

Cyclopentenone prostaglandins (PGs) inhibit the replication of a wide variety of enveloped DNA and RNA viruses. The antiviral activity is as sociated with alterations in the synthesis, maturation, and intracellu lar translocation of viral proteins. In the present report, we describ e the effects of cyclopentenone PGs PGA(1) and Delta(12)-PGJ(2) on pol iovirus (PV) replication in HeLa cells, Both PGs were found to inhibit PV replication dose dependently, Virus yield was significantly reduce d at nontoxic concentrations, which did not suppress RNA or protein sy nthesis in uninfected or PV-infected cells, Both the pattern of PV pro teins synthesized and the kinetics of viral protein synthesis and degr adation appeared to be similar in PGA(1)-treated cells and control cel ls. Antiviral PGs have been shown to selectively inhibit virus protein synthesis during the replication of several viruses, including vesicu lar stomatitis virus (VSV), and this effect has been recently associat ed with the induction of a 70-kDa heat shock protein (HSP70), PGA(1) a nd Delta(12)-PGJ(2) were found to induce HSP70 synthesis in uninfected or VSV-infected HeLa cells, PV infection gas found to inhibit PG-indu ced HSP70 synthesis in these cells, suggesting that the lack of abilit y of cyclopentenone PGs to block PV protein synthesis could be related to an impaired heat shock response in PV-infected cells, The finding that PV protein synthesis was not inhibited by PGs suggests that cyclo pentenone PGs could interfere with a late event in the virus replicati on cycle, such as protein assembly and maturation of PV virions.