title: Monoclonal antibody neutralization escape mutants of respiratory syncytial virus with unique alterations in the attachment (G) protein.
abstract: Five monoclonal antibody (MAb) neutralization escape mutants of respiratory syncytial virus (RSV) were produced by growing the Long strain RSV (group A virus) in the presence of a neutralizing, group cross-reactive MAb specific for the attachment protein (G). Four viruses (RSV-2, -6, -14 and -15) had amino acid replacements clustered within a highly conserved centrally located 13 amino acid region (position 164-176). Reactivity with group A-specific MAbs and with polyclonal anti-G serum was maintained and growth kinetics were unaffected. An additional virus (RSV-3) had four amino acid substitutions in the cytoplasmic tail and transmembrane region of G, and had restricted growth and formed small syncytia. Immunofluorescent and Western blot analysis indicated that G protein was not membrane associated and had reduced incorporation into the virion, thereby escaping neutralization by L9 and polyclonal anti-G serum. The predominant form of G produced by RSV-3 was found in infected cell supernatants, consistent with the size of secreted G.
authors.affiliation: University of Rochester School of Medicine and Dentistry and Rochester General Hospital, New York 14621, USA. ewalsh@rghnet.edu
authors.forename: E E
authors.initials: EE
authors.lastname: Walsh
authors.forename: A R
authors.initials: AR
authors.lastname: Falsey
authors.forename: W M
authors.initials: WM
authors.lastname: Sullender
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001287:Attachment Sites, Microbiological; D001483:Base Sequence; D015153:Blotting, Western; D019084:Fluorescent Antibody Technique, Indirect; D015707:HN Protein; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G