Monoclonal antibody neutralization escape mutants of respiratory syncytial virus with unique alterations in the attachment (G) protein.
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.
Walsh
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EE
University of Rochester School of Medicine and Dentistry and Rochester General Hospital, New York 14621, USA. ewalsh@rghnet.edu
Falsey
A R
AR
Sullender
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WM
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
D000911:Antibodies, Monoclonal; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G