title: Inhibition of Sindbis virus replication by cyclopentenone prostaglandins: a cell-mediated event associated with heat-shock protein synthesis.
abstract: Cyclopentenone prostaglandins (PGs) have been shown to inhibit the replication of several DNA and RNA viruses. Here we report on the effect of prostaglandin A1 (PGA1) on the multiplication of a positive strand RNA virus, Sindbis virus, in Vero cells under one-step multiplication conditions. PGA1 was found to inhibit Sindbis virus production dose-dependently, and virus yield was reduced by more than 90% at the concentration of 8 micrograms/ml, which was non-toxic to the cells and did not inhibit DNA, RNA or protein synthesis in Vero cells. The cyclopentenone prostaglandin delta 12-PGJ2 was also shown to be a potent inhibitor of Sindbis virus replication. Virus-induced reduction of [3H]uridine uptake by cells was partially prevented by PGA1 treatment, which also caused a 1 h delay in the peak of virus RNA synthesis. SDS-PAGE analysis of [35S]methionine-labeled proteins showed that PGA1 moderately inhibited the synthesis of the viral structural proteins E1, E2 and C, and induced the synthesis of a 72 kDa M(r) protein, identified as a heat-shock protein related to the HSP70 group, in both virus-infected and uninfected cells. Actinomycin D treatment completely prevented PGA1-antiviral activity, indicating that a cellular product is responsible for this action. PGA1-induced HSP70 is a good candidate for this role.
authors: Institute of Microbiology, School of Medicine, University La Sapienza, Rome, Italy.
authors: P
authors: P
authors: Mastromarino
authors: C
authors: C
authors: Conti
authors: R
authors: R
authors: Petruzziello
authors: A
authors: A
authors: De Marco
authors: F
authors: F
authors: Pica
authors: M G
authors: MG
authors: Santoro
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004279:DNA, Viral / Q000096:biosynthesis; D003609:Dactinomycin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D015151:Immunoblotting; D011454:Prostaglandins A / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis; D012845:Sindbis Virus / Q000187:drug effects* / Q000502:physiology; D014529:Uridine / Q000378:metabolism; D014709:Vero Cells; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006360:Heat-Shock Proteins; D011454:Prostaglandins A; D012367:RNA, Viral; D014764:Viral Proteins; D003609:Dactinomycin; C100573:prostaglandin A1; D014529:Uridine