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PMID: 2470922 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function.

Journal of virology ·Vol. 63 ·No. 7 ·1989-07-00 ·Pages 2941-50

Beeler JA, van Wyke Coelingh K

Abstract

Eighteen neutralizing monoclonal antibodies (MAbs) specific for the fusion glycoprotein of the A2 strain of respiratory syncytial virus (RSV) were used to construct a detailed topological and operational map of epitopes involved in neutralization and fusion. Competitive binding assays identified three nonoverlapping antigenic sites (A, B, and C) and one bridge site (AB). Thirteen MAb-resistant mutants (MARMs) were selected, and the neutralization patterns of the MAbs with either MARMs or RSV clinical strains identified a minimum of 16 epitopes. MARMs selected with antibodies to six of the site A and AB epitopes displayed a small-plaque phenotype, which is consistent with an alteration in a biologically active region of the F molecule. Analysis of MARMs also indicated that these neutralization epitopes occupy topographically distinct but conformationally interdependent regions with unique biological and immunological properties. Antigenic variation in F epitopes was examined by using 23 clinical isolates (18 subgroup A and 5 subgroup B) in cross-neutralization assays with the 18 anti-F MAbs. This analysis identified constant, variable, and hypervariable regions on the molecule and indicated that antigenic variation in the neutralization epitopes of the RSV F glycoprotein is the result of a noncumulative genetic heterogeneity. Of the 16 eptiopes, 8 were conserved on all or all but 1 of 23 subgroup A or subgroup B clinical isolates.

MeSH Terms
Animals Antibodies, Monoclonal Cell Line Enzyme-Linked Immunosorbent Assay Epitopes/analysis Female Hybridomas/immunology Mice Mice, Inbred BALB C/immunology Mutation Neutralization Tests Respiratory Syncytial Viruses/genetics,physiology Viral Fusion Proteins/genetics,immunology,physiology
Chemicals
Antibodies, Monoclonal Epitopes Viral Fusion Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Beeler J A
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
van Wyke Coelingh K
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.63.7.2941-2950.1989
Published
1989-07-00
Pages
2941-50
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC250848
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.63.7.2941-2950.1989 PMC Full Text View journal details
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