C. Amici et al., SELECTIVE-INHIBITION OF VIRUS PROTEIN-SYNTHESIS BY PROSTAGLANDIN A(1)- A TRANSLATIONAL BLOCK ASSOCIATED WITH HSP70 SYNTHESIS, Journal of virology, 68(11), 1994, pp. 6890-6899
Cyclopentenone prostaglandins are potent inhibitors of virus replicati
on. The antiviral activity has been associated with the induction of 7
0-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 prostaglandn A(1) (PGA(1)), 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 in
dicated by the following (i) PGA(1) had no effect on SV primary transc
ription, and a dramatic decrease in the abundance of SV mRNA occurred
only at later stages of infection; and (ii) treatment with PGA(1) star
ted at 6 h postinfection, at which time SV mRNA had already accumulate
d in infected cells, did not suppress the levels of NP mRNA, but it re
duced the amount of ribosome-bound NP mRNA and caused a dramatic decre
ase in the level of genomic RNA. The PGA(1)-induced block of SV protei
n synthesis appeared to be cell mediated, since it was prevented by ac
tinomycin D, while PGA(1) had no effect on SV mRNA translation in vitr
o. The possibility that HSP70 could be a mediator of the antiviral eff
ect is suggested by the fact that treatment with other classical induc
ers 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 s
ynthesis was not inhibited by PGA(1) in murine Friend erythroleukemic
cells, which lack the ability to induce HSP70 expression in response t
o PGA(1).