Inhibition of virus protein glycosylation as the mechanism of the antiviral action of prostaglandin A in Sendai virus-infected cells.
Prostaglandin A (PGA) inhibits Sendai virus replication at doses non-toxic to uninfected cells. In this report, the antiviral action of PGA was found to be associated with specific alterations of viral protein synthesis. SDS-PAGE analysis of [35S]methionine-labelled proteins showed that while the non-glycosylated viral polypeptides (P, NP and M) were normally synthesized in PGA1-treated cells, the viral glycoproteins HN and F0 were not detected. Two new polypeptides of Mr respectively 4000 and 1000 lower than the HN and F0 proteins were instead detected. The results suggest that these new polypeptides are defectively glycosylated forms of HN and F0. In fact PGA1 was found selectively to inhibit glucosamine incorporation into Sendai virus-infected cells, but not in uninfected cells. Moreover, in infected cells the inhibition of glucosamine incorporation appeared to be selective towards viral polypeptides. This effect was not due to a decreased uptake of glucosamine from the cells after PGA1 treatment. The results also show that the PGA1-induced alteration of the HN protein caused a loss of its biological function and prevented the insertion of this protein into the cell membrane, thereby blocking virus maturation. Finally, a polypeptide of Mr 74K, the synthesis of which was induced by PGA1, appeared to be a possible mediator of PGA1 antiviral action.
Santoro
M G
MG
Institute of Experimental Medicine, C.N.R., Rome, Italy.
Amici
C
C
Elia
G
G
Benedetto
A
A
Garaci
E
E
D001345:Autoradiography; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D015151:Immunoblotting; D010222:Parainfluenza Virus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011454:Prostaglandins A / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D006023:Glycoproteins; D011454:Prostaglandins A; D012367:RNA, Viral; D014764:Viral Proteins; D003609:Dactinomycin; D005944:Glucosamine