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 PGAm-treated cells, the viral glycoproteins HN and Fo were not detected. Two new polypeptides ofMr respectively 4000 and 1000 lower than the HN and Fo proteins were instead etected. The results suggest that these new polypeptides are defectively glycosylated forms of HN and Fo. In fact PGA1 was found selectively to inhibit glucosamine incorporation i to Sendal 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 PGAI treatment. The results also show that the PGAl-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 ofMT 74K, the synthesis of which was induced by PGA1, appeared to be a possible mediator of PGA1 antiviral action