Processing of gPr92env, the precursor to the glycoproteins of Rous sarcoma virus: use of inhibitors of oligosaccharide trimming and glycoprotein transport.
A number of aspects of the processing of gPr92env, the precursor to the viral glycoproteins gp85 and gp35 of Rous sarcoma virus (RSV), have been studied. First, the kinetics of gPr92env processing have been examined, revealing that the precursor is overproduced in the infected cell and only a small percentage (less than 5%) is converted into mature glycoprotein in virus particles. Second, the effects of inhibitors of intracellular transport (monensin) and oligosaccharide trimming (N-methyl-1-deoxynojirimycin (MdN) and bromoconduritol (BC) ) on the processing of gPr92env have been examined. It could be shown with all three inhibitors that proteolytic cleavage of gPr92env could occur although oligosaccharide trimming was inhibited. The aberrant cleavage products, gp75mon and gp30mon, produced in the presence of monensin, carry oligosaccharides where only 1-3 mannose residues have been removed in comparison to the precursor gPr92env (this latter carries predominantly Man9(GlcNAc)2). Virus particles containing the aberrant glycoproteins were released in virtually normal amounts and were infectious. In the presence of MdN and BC, viral glycoprotein precursors carrying three (MdN) or one (BC) glucose on the high-mannose oligosaccharide could be detected intracellularly. The aberrant precursors could be proteolytically cleaved to gp80MdN and gp75BC which are equivalent to gp85 but carry the smaller glucose-containing high-mannose oligosaccharides instead of the large, complex, sialidated oligosaccharides of mature glycoprotein. In the presence of MdN, the abnormal glycoproteins were incorporated into virions which were fully infectious.
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives*; D001358:Avian Sarcoma Viruses / Q000378:metabolism*; D001693:Biological Transport, Active; D002478:Cells, Cultured; D053138:Cyclohexenes; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D009844:Oligosaccharides / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis*; D014771:Virion / Q000378:metabolism
D053138:Cyclohexenes; D006023:Glycoproteins; D009844:Oligosaccharides; D014764:Viral Proteins; D017485:1-Deoxynojirimycin; C036388:6-bromoconduritol; D007294:Inositol; D005944:Glucosamine; C033424:N-methyldeoxynojirimycin