The effect of deoxymannojirimycin on the processing of the influenza viral glycoproteins.
Deoxymannojirimycin (dMM) was tested as an inhibitor of the processing of the oligosaccharide portion of viral and cellular N-linked glycoproteins. The NWS strain of influenza virus was grown in MDCK cells in the presence of various amounts of dMM, and the glycoproteins were labeled by the addition of 2-[3H]mannose to the medium. At levels of 10 micrograms/ml dMM or higher, most of the viral glycopeptides became susceptible to digestion by endoglucosaminidase H, and the liberated oligosaccharide migrated mostly like a Hexose9GlcNAc on a calibrated column of Bio-Gel P-4. This oligosaccharide was characterized as a typical Man9GlcNAc by a variety of chemical and enzymatic procedures. Deoxymannojirimycin gave rise to similar oligosaccharide structures in the cellular glycoproteins. In both the viral and the cellular glycoproteins, this inhibitor caused a significant increase in the amount of [3H]mannose present in the glycoproteins. Deoxymannojirimycin did not inhibit the incorporation of [3H]leucine into protein in MDCK cells, nor did it affect the yield or infectivity of NWS virus particles. However, its effect on mannose incorporation into lipid-linked saccharides depended on the incubation time, the virus strain, and the cell line. Thus, high concentrations of dMM showed some inhibition of mannose incorporation into lipid-linked oligosaccharides with the NWS strain in a 3-h incubation, but no inhibition was observed after 48 h of incubation. On the other hand, the PR8 strain was much more sensitive to dMM inhibition, and mannose incorporation into lipid-linked oligosaccharides was strongly inhibited when the virus was raised in chick embryo cells, but less inhibition was observed when this virus was grown in MDCK cells. Nevertheless, in these cases also, the major oligosaccharide structure in the glycoproteins was the Man9GlcNAc2 species.
D017485:1-Deoxynojirimycin; D000470:Alkaloids / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D007212:Indolizines; D007930:Leucine / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D008358:Mannose / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism*; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D000470:Alkaloids; D000998:Antiviral Agents; D005944:Glucosamine; D006023:Glycoproteins; D007212:Indolizines; D007930:Leucine; D008055:Lipids; D008358:Mannose; D009844:Oligosaccharides; D014764:Viral Proteins; C037806:castanospermine; D054836:Indolizidines