On the role of oligosaccharide trimming in the maturation of Sindbis and influenza virus.
The alpha-glucosidase inhibitor bromoconduritol inhibits the formation of the N-linked, complex-type oligosaccharides of the glycoproteins from influenza viruses (fowl plague virus, influenza virus PR-8) and from sindbis virus. Viral glycoproteins produced in bromoconduritol-treated chicken-embryo and baby-hamster kidney cells are fully glycosylated, but accumulate N-linked, high-mannose oligosaccharides of the composition Glc1Manx (GlcNAc)2 (x = 7, 8, and 9). Other alpha-glucosidase inhibitors (nojirimycin, deoxynojirimycin, acarbose) were not specific inhibitors of oligosaccharide processing under the conditions used in the present investigation. In bromoconduritol-treated, sindbis virus-infected chicken-embryo and baby-hamster kidney cells, the sindbis glycoproteins are metabolically stable. Specific proteolytic cleavage of the polyprotein precursors to form E2 and E1 occurs in bromoconduritol-treated chicken-embryo cells, but cleavage of PE2 to E2 is prevented in the infected baby-hamster kidney cells. Yet, release of infectious sindbis virus particles is inhibited in both cell types indicating that the formation of complex oligosaccharides is required for a late step in virus formation. The release of virus particles from influenza virus PR-8-infected bromoconduritol-treated chicken-embryo cells is not inhibited, and virus with only high-mannose oligosaccharides is formed. In contrast, when chicken-embryo cells were infected with the influenza virus fowl plague virus, release of infectious particles was inhibited. The fowl plague virus hemagglutinin is cleaved in chicken-embryo cells, in contrast to the hemagglutinin of the PR-8 virus. However, the cleavage products HA1 and HA2 do not reach the cell surface. In addition, or as a consequence, HA1 and HA2 are proteolytically broken down, whereas uncleaved hemagglutinin of PR-8 appeared metabolically stable. These results may explain the decrease in formation of fowl plague virus particles and the lack of effect on PR-8 virus in bromoconduritol-treated cells. This work thus shows different biological roles for oligosaccharide processing.
D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D006224:Cricetinae; D053138:Cyclohexenes; D006023:Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D009980:Influenza A virus / Q000187:drug effects / Q000254:growth & development*; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney; D009844:Oligosaccharides / Q000302:isolation & purification / Q000378:metabolism*; D012845:Sindbis Virus / Q000187:drug effects / Q000254:growth & development*; D014764:Viral Proteins / Q000096:biosynthesis* / Q000302:isolation & purification
D053138:Cyclohexenes; D006023:Glycoproteins; D009844:Oligosaccharides; D014764:Viral Proteins; C036388:6-bromoconduritol; D007294:Inositol; D006026:Glycoside Hydrolases