Membrane cofactor protein with different types of N-glycans can serve as measles virus receptor.
Membrane cofactor protein (MCP) has been shown to act as a cellular receptor for measles virus. In previous binding studies we demonstrated a direct interaction between the measles virus H protein and MCP. The binding was shown to be independent of the O-glycans but dependent on the N-glycans of MCP. To elucidate the role of N-glycans for the receptor function of MCP, the effect of the glycosylation inhibitors tunicamycin (TM) and 1-deoxymannojirimycin (DMJ) was analyzed. TM which prevents N-glycosylation has been reported to inhibit the expression of functional measles virus receptors. Here we show that MCP lacking all N-glycans was detectable on the surface of Vero cells, although in a reduced amount. Therefore, the lack of receptor activity cannot be explained by intracellular degradation or defective transport. In the presence of DMJ, a mannosidase I inhibitor, MCP is synthesized with N-glycans of the high-mannose type in contrast to the complex oligosaccharides present on MCP of untreated cells. Both MCP with mannose-rich and MCP with complex N-glycans were recognized by measles virus H protein in an in vitro binding assay. They both could also serve as receptors for the infection of cultured Vero cells, arguing against a direct binding of virus to a carbohydrate moiety within the N-glycans of MCP. We propose that N-linked oligosaccharides are required to maintain a conformation-dependent receptor determinant of MCP.
Maisner
A
A
Institut für Virologie, Philipps-Universität Marburg, Germany.
Herrler
G
G
D017485:1-Deoxynojirimycin; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006031:Glycosylation; D008358:Mannose; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D009844:Oligosaccharides; D011134:Polysaccharides / Q000032:analysis*; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D014415:Tunicamycin; D014709:Vero Cells
D015703:Antigens, CD; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011134:Polysaccharides; D011991:Receptors, Virus; D014415:Tunicamycin; D017485:1-Deoxynojirimycin; D008358:Mannose