Relationship between the loss of neutralizing antibody binding and fusion activity of the F protein of human respiratory syncytial virus.
To elucidate the relationship between resistance to HRSV neutralizing antibodies directed against the F protein and the fusion activity of the F protein, a recombinant approach was used to generate a panel of mutations in the major antigenic sites of the F protein. These mutant proteins were assayed for neutralizing mAb binding (ch101F, palivizumab, and MAb19), level of expression, post-translational processing, cell surface expression, and fusion activity. Functional analysis of the fusion activity of the panel of mutations revealed that the fusion activity of the F protein is tolerant to multiple changes in the site II and IV/V/VI region in contrast with the somewhat limited spectrum of changes in the F protein identified from the isolation of HRSV neutralizing antibody virus escape mutants. This finding suggests that aspects other than fusion activity may limit the spectrum of changes tolerated within the F protein that are selected for by neutralizing antibodies.
Liu
Changbao
C
Centocor R&D, Inc., Radnor, Pennsylvania 19087, USA. Cliu12@cntus.jnj.com
Day
Nicole D
ND
Branigan
Patrick J
PJ
Gutshall
Lester L
LL
Sarisky
Robert T
RT
Del Vecchio
Alfred M
AM
D000911:Antibodies, Monoclonal / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D006801:Humans; D009154:Mutation; D009500:Neutralization Tests; D000069455:Palivizumab; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins; D000069455:Palivizumab