INHIBITION OF ROTAVIRUS REPLICATION BY PROSTAGLANDIN-A - EVIDENCE FORA BLOCK OF VIRUS MATURATION

Rotaviruses are recognized as the leading cause of severe viral gastro enteritis in young children and in immunocompromised patients. Cyclope ntenone prostaglandins possess antiviral activity against several sing le-strand RNA viruses; therefore, the effect of prostaglandin A(1) (PG A(1)) on SA-11 simian rotavirus infection was investigated in cultured cells. PGA(1) potently inhibited SA-11 rotavirus replication. Whereas it did not affect virus adsorption or penetration, PGA(1) partially i nhibited VP4 and VP7 synthesis and selectively reduced glucosamine inc orporation into the NSP4 viral enterotoxin. Electron microscopy analys is showed that, despite normal formation of cytoplasmic inclusions and budding of particles into the rough endoplasmic reticulum, virus matu ration was impaired in PGA(1)-treated cells, with most of the virus pa rticles remaining in the membrane-enveloped intermediate form. Because prostaglandins are used clinically as cytoprotective drugs for gastri c ulcers, these observations offer new perspectives in the search for therapeutic agents for rotavirus-induced gastroenteritis.