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 beenassociated with the induction of 70-kDa heat shock protein (HSP70) synthesis. In this report, we describe thatin 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 elfect on SVprimary transcription, and a dramatic decrease in the abundance of SV mRNA occurred only at later stagesof infection; and (ii) treatment with PGA1 started at 6 h postinfection, at which time SV mRNA had alreadyaccumulated in infected cells, did not suppress the levels of NP mRNA, but it reduced the amount ofribosome-bound NP mRNA and caused a dramatic decrease in the level of genomic RNA. The PGAl-inducedblock of SV protein synthesis appeared to be cell mediated, since it was prevented by actinomycin D, whilePGA, had no effect on SV mRNA translation in vitro. The possibility that HSP70 could be a mediator of theantiviral effect is suggested by the fact that treatment with other classical inducers of HSP70, including sodiumarsenite, cadmium, and heat shock at 42°C for 5 h, also selectively prevented SV protein synthesis as long asheat shock protein synthesis occurred. Moreover, SV protein synthesis was not inhibited by PGA1 in murineFriend erythroleukemic cells, which lack the ability to induce HSP70 expression in response to PGA1.