Regulation of susceptibility and cell surface receptor for the B-lymphotropic papovavirus by N glycosylation.
The host range of the B-lymphotropic papovavirus (LPV) in cultured human cells is limited to a few B-lymphoma-derived cell lines. The constitutively expressed cell surface receptor for the virus is a major determinant restricting the LPV host range (G. Haun, O. T. Keppler, C. T. Bock, M. Herrmann, H. Zentgraf, and M. Pawlita, J. Virol. 67:7482-7492, 1993). Here we show that human B-lymphoma cells with low-level susceptibility are rendered highly susceptible to LPV infection by pretreatment with the N glycosylation inhibitor tunicamycin but remain nonsusceptible to infection by the related polyomavirus simian virus 40. Among the selective N glycosylation processing inhibitors, deoxymannojirimycin, but not deoxynojirimycin, swainsonine, or castanospermine, could mimic the effect of tunicamycin. Tunicamycin treatment also induced a drastic enhancement of the cells' LPV-binding capacity, indicating that the induction of LPV susceptibility might be mediated by an increase in the number of functional cell surface receptors and/or by increased receptor affinity. Sialidase sensitivity of the tunicamycin-induced LPV receptor showed that oligosaccharides carrying terminal sialic acids are necessary for binding and are likely to be O linked. The constitutive LPV receptor is also sialic acid dependent, which points to a possible identity with the sialic acid-dependent tunicamycin-induced LPV receptor. We conclude that removal or modification of certain N-linked oligosaccharides in human B-lymphoma cells can enhance expression or functional activity of the sialylated LPV receptor.
Keppler
O T
OT
Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Herrmann
M
M
Oppenländer
M
M
Meschede
W
W
Pawlita
M
M
D001402:B-Lymphocytes / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D006031:Glycosylation; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000821:virology; D019158:N-Acetylneuraminic Acid; D027383:Papillomaviridae / Q000502:physiology*; D027382:Polyomaviridae; D011991:Receptors, Virus / Q000032:analysis* / Q000502:physiology; D012794:Sialic Acids / Q000378:metabolism; D017026:Swainsonine / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D054836:Indolizidines
D007212:Indolizines; D019158:N-Acetylneuraminic Acid; D011991:Receptors, Virus; D012794:Sialic Acids; D017026:Swainsonine; D014415:Tunicamycin; C037806:castanospermine; D054836:Indolizidines