Fusion mutants of Newcastle disease virus selected with monoclonal antibodies to the hemagglutinin-neuraminidase.
The Australia-Victoria (AV) isolate of Newcastle disease virus (NDV) induces fusion from within but not fusion from without. L1, a neuraminidase (NA)-deficient virus derived from AV, has the opposite fusion phenotype from the wild-type virus. It fails to induce the former mode of fusion, but has gained a limited ability to promote the latter. Monoclonal antibodies to antigenic site 23 on the hemagglutinin-neuraminidase (HN) glycoprotein have previously been shown to select variants of the AV isolate that have altered NA activity or receptor-binding affinity. By using an antibody to this site, variants of L1 have been selected. Three of the variants have gained an increased affinity for sialic acid-containing receptors, as evidenced by the resistance of their hemagglutinating activity to the presence of reduced amounts of sialic acid on the surface of chicken erythrocytes. All four variants still have very low levels of NA activity, comparable to that of the parent virus, L1. The alteration in receptor-binding affinity results in a decreased potential for elution from cellular receptors and correlates with an increased ability to promote both modes of fusion. A single amino acid substitution in the HN protein of each variant, responsible for its escape from neutralization, has been identified. These studies identify two HN residues, 193 and 203, at which monoclonal antibody-selected substitution influences the receptor recognition properties of NDV and may influence its ability to promote syncytium formation.
Iorio
R M
RM
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Glickman
R L
RL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology; D002459:Cell Fusion; D002478:Cells, Cultured; D014644:Genetic Variation; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000235:genetics* / Q000276:immunology; D009522:Newcastle disease virus / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D011991:Receptors, Virus / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D011991:Receptors, Virus; D012794:Sialic Acids; D014760:Viral Fusion Proteins; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid