Effect of combined alpha IFN and prostaglandin A1 treatment on vesicular stomatitis virus replication and heat shock protein synthesis in epithelial cells.
The antiviral activity of prostaglandin A (PGA) and interferons (IFNs) has been widely described. In the present report, we investigated the effect of combined alpha IFN and PGA1 treatment on vesicular stomatitis virus (VSV) replication and on heat shock protein (HSP) induction in monkey epithelia cells. In uninfected cells, PGA1 caused a dose-dependent induction of HSP70, HSP90 and HSP110, while alpha IFN did not affect HSP synthesis. Alpha-IFN suppressed VSV replication dose-dependently, even when cells were treated after virus infection. VSV protein synthesis was not affected by alpha IFN, indicating a block at the level of virus assembly or maturation. PGA1 caused a dose-dependent inhibition of VSV replication, and suppressed VSV protein synthesis at concentrations which induced the synthesis of high levels of HSP70. The combined treatment with low doses of alpha IFN or PGA1, which only moderately inhibited VSV replication when administered separately, was found to suppress VSV production by more than 95%, and resulted in a 3-fold increase of HSP70 synthesis as compared to PGA1 alone. These results demonstrate a co-operative effect of PGA1 and alpha IFN against VSV infection and suggest that alpha IFN can potentiate the cellular response to HSP induction in virus-infected cells.
Pica
F
F
Institute of Experimental Medicine, CNR, Rome, Italy.
Rossi
A
A
Santirocco
N
N
Palamara
A
A
Garaci
E
E
Santoro
M G
MG
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004347:Drug Interactions; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D000882:Haplorhini; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C097205:HSPH1 protein, human; D006360:Heat-Shock Proteins; D016898:Interferon-alpha; D011454:Prostaglandins A; D011506:Proteins; D014764:Viral Proteins; C100573:prostaglandin A1