Processing of N-linked oligosaccharides on the measles virus glycoproteins: importance for antigenicity and for production of infectious virus particles.
The envelope of measles virus (MV) particles contains two viral glycoproteins, the haemagglutinin (H) and the fusion (F) protein, which together induce the entry of MV into cells. In the present study, we investigated the role of oligosaccharide processing for the function and antigenicity of the MV glycoproteins by means of glycosidase inhibitors. Golgi alpha-mannosidase inhibitors (1-deoxymannojirimycin and swainsonine) prevented the oligosaccharides on the MV glycoproteins from obtaining Endo H resistance, but that did not appear to influence in vitro MV infections, indicating that conversion of oligosaccharide chains into the complex form was not required for the function of the MV glycoproteins. The alpha-glucosidase inhibitor castanospermine (CSP) quantitatively reduced the production of infectious MV particles in cells infected with both vaccine strain and wild-type MV. CSP reduced the detection of the MV F protein by certain monoclonal antibodies (MAbs) that appeared to recognize nonlinear epitopes. CSP also inhibited syncytium formation in MV infected cells, but did not affect MV induced CD46 downregulation, suggesting that CSP primarily influenced the F protein. We propose that CSP induces aberrant folding of MV glycoproteins in a manner that influences their function and antigenicity.
Bolt
G
G
Department of Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Denmark. g.bolt@immi.ku.dk
Pedersen
I R
IR
Blixenkrone-Møller
M
M
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D008361:Mannosidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008459:Measles virus / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017026:Swainsonine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014760:Viral Fusion Proteins / Q000276:immunology / Q000378:metabolism*; D014771:Virion / Q000502:physiology; D000520:alpha-Glucosidases / Q000378:metabolism*; D043323:alpha-Mannosidase; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D065089:Glycoside Hydrolase Inhibitors; D006389:Hemagglutinins, Viral; D007212:Indolizines; D008361:Mannosidases; D009844:Oligosaccharides; D017026:Swainsonine; D014760:Viral Fusion Proteins; D000520:alpha-Glucosidases; D043323:alpha-Mannosidase; C032397:hemagglutinin protein G, measles virus; C037806:castanospermine; D054836:Indolizidines