Inhibition of poliovirus replication by prostaglandins A and J in human cells.
Cyclopentenone prostaglandins (PGs) inhibit the replication of a wide variety of enveloped DNA and RNA viruses. The antiviral activity is associated with alterations in the synthesis, maturation, and intracellular translocation of viral proteins. In the present report, we describe the effects of cyclopentenone PGs PGA1 and delta 12-PGJ2 on poliovirus (PV) replication in HeLa cells. Both PGs were found to inhibit PV replication dose dependently. Virus yield was significantly reduced at nontoxic concentrations, which did not suppress RNA or protein synthesis in uninfected or PV-infected cells. Both the pattern of PV proteins synthesized and the kinetics of viral protein synthesis and degradation appeared to be similar in PGA1-treated cells and control cells. Antiviral PGs have been shown to selectively inhibit virus protein synthesis during the replication of several viruses, including vesicular stomatitis virus (VSV), and this effect has been recently associated with the induction of a 70-kDa heat shock protein (HSP70). PGA1 and delta 12-PGJ2 were found to induce HSP70 synthesis in uninfected or VSV-infected HeLa cells. PV infection was found to inhibit PG-induced HSP70 synthesis in these cells, suggesting that the lack of ability 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 cyclopentenone PGs could interfere with a late event in the virus replication cycle, such as protein assembly and maturation of PV virions.
Conti
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C
Institute of Microbiology, University La Sapienza, Rome, Italy.
Mastromarino
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P
Tomao
P
P
De Marco
A
A
Pica
F
F
Santoro
M G
MG
D000998:Antiviral Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D017955:Poliovirus / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000031:analogs & derivatives; D011454:Prostaglandins A / Q000494:pharmacology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D018840:HSP70 Heat-Shock Proteins; D011454:Prostaglandins A; D011465:Prostaglandins, Synthetic; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D015230:Prostaglandin D2; C100573:prostaglandin A1