Antiviral effect of cyclopentenone prostaglandins on vesicular stomatitis virus replication.
Prostaglandins are potentially useful antiviral agents, however their mechanism of action is unclear. Recent evidence suggests that RNA transcription of vesicular stomatitis virus (VSV) is inhibited by prostaglandins (Bader and Ankel, J. Gen. Virol. 71, 2823-2832, 1990). Prostaglandins are known to have multiple effects on cells which may or may not be related to their antiviral action. We examined the effects of prostaglandins on cells and on VSV RNA polymerase in vitro to seek the mechanism of antiviral action. Actinomycin D inhibited cellular RNA synthesis but failed to block the antiviral activity of prostaglandins on VSV. Thus induction of host cell RNA transcription is not involved in the antiviral action. Neither modulation of the cellular glutathione level by prostaglandins nor formation of prostaglandin-glutathione conjugates was required for the antiviral action. The relative inhibition of VSV RNA polymerase in vitro by prostaglandins with different structures correlated to inhibition of VSV replication in infected cells. This result indicates that the same step in VSV replication is inhibited by prostaglandins both in the in vitro RNA polymerase assay and in the infected cell.
Parker
J
J
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226, USA.
Ahrens
P B
PB
Ankel
H
H
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003517:Cyclopentanes / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D007939:Leukemia L1210 / Q000378:metabolism / Q000821:virology; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000502:physiology; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D003517:Cyclopentanes; D011453:Prostaglandins; D011454:Prostaglandins A; D014764:Viral Proteins; C037112:9-deoxy-delta-9-prostaglandin D2; D012313:RNA; D012321:DNA-Directed RNA Polymerases; D005978:Glutathione; C100008:prostaglandin A2; C013905:cyclopentenone; D015230:Prostaglandin D2