Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus.
The majority of neutralizing monoclonal antibodies (MAbs) to the haemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus prevent attachment of the virus to cellular receptors and inhibits virion-induced fusion from without (FFWO) and fusion from within (FFWI) mediated by the virus glycoprotein-laden infected cell surface. For these antibodies, the inhibition of fusion is presumed to be the result of the prevention of HN-mediated bridging of potential fusion partners. MAbs against antigenic sites 3 and 4 neutralize virus infectivity, but by a mechanism other than the prevention of attachment, the exact nature of which remains to be established. Antibodies to both of these sites effectively inhibit virion-induced FFWO, even when the inducing virus is not infectious. This is consistent with the mechanism of neutralization of these MAbs involving the inhibition of an early, post-attachment step in infection. MAbs to site 3 also inhibit FFWI, but those to site 4 do not, even when added at high concentrations. This suggests that the requirement for HN may be different in the two modes of fusion. The epitopes recognized by MAbs to sites 3 and 4 have been delineated by the identification of individual nucleotide substitutions in the HN genes of neutralization escape variants. Some of the deduced amino acid substitutions result in additional N-linked glycosylation sites in HN, which are utilized and presumably account for the escape from neutralization.
Iorio
R M
RM
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Glickman
R L
RL
Sheehan
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002459:Cell Fusion / Q000276:immunology*; D002478:Cells, Cultured; D002642:Chick Embryo; D000939:Epitopes / Q000276:immunology; D005347:Fibroblasts / Q000382:microbiology; D006031:Glycosylation; D015707:HN Protein / Q000276:immunology*; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009522:Newcastle disease virus / Q000276:immunology* / Q000472:pathogenicity; D014771:Virion / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015707:HN Protein; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase