Inhibition of Sindbis virus replication by cyclopentenone prostaglandins: a cell-mediated event associated with heat-shock protein synthesis.
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.
Mastromarino
P
P
Institute of Microbiology, School of Medicine, University La Sapienza, Rome, Italy.
Conti
C
C
Petruzziello
R
R
De Marco
A
A
Pica
F
F
Santoro
M G
MG
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*
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