Selective inhibition of virus protein synthesis by prostaglandin A1: a translational block associated with HSP70 synthesis.
Cyclopentenone prostaglandins are potent inhibitors of virus replication. The antiviral activity has been associated with the induction of 70-kDa heat shock protein (HSP70) synthesis. In this report, we describe that in African green monkey kidney cells infected with Sendai virus (SV) and treated with prostaglandin A1 (PGA1), SV protein synthesis was selectively blocked as long as HSP70 was being synthesized by the host cell. The block appeared to be at the translational level, as indicated by the following (i) PGA1 had no effect on SV primary transcription, and a dramatic decrease in the abundance of SV mRNA occurred only at later stages of infection; and (ii) treatment with PGA1 started at 6 h postinfection, at which time SV mRNA had already accumulated in infected cells, did not suppress the levels of NP mRNA, but it reduced the amount of ribosome-bound NP mRNA and caused a dramatic decrease in the level of genomic RNA. The PGA1-induced block of SV protein synthesis appeared to be cell mediated, since it was prevented by actinomycin D, while PGA1 had no effect on SV mRNA translation in vitro. The possibility that HSP70 could be a mediator of the antiviral effect is suggested by the fact that treatment with other classical inducers of HSP70, including sodium arsenite, cadmium, and heat shock at 42 degrees C for 5 h, also selectively prevented SV protein synthesis as long as heat shock protein synthesis occurred. Moreover, SV protein synthesis was not inhibited by PGA1 in murine Friend erythroleukemic cells, which lack the ability to induce HSP70 expression in response to PGA1.
Amici
C
C
Department of Experimental Medicine, University of Tor Vergata, Rome, Italy.
Giorgi
C
C
Rossi
A
A
Santoro
M G
MG
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D010222:Parainfluenza Virus 1, Human / Q000378:metabolism*; D011454:Prostaglandins A / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis*
D018840:HSP70 Heat-Shock Proteins; D011454:Prostaglandins A; D014764:Viral Proteins; C100573:prostaglandin A1