Location of antigenic sites on the three-dimensional structure of the influenza N2 virus neuraminidase.
Sequence analysis of the neuraminidase (NA) genes of influenza virus X-7(F1) and of 12 variants selected with monoclonal antibodies has been used to define in physical terms the antigenic structure of this NA, which was operationally established by R. G. Webster, L. E. Brown, and W. G. Laver (1984, Virology 135, 30-42). X-7(F1) is a reassortant virus containing the NA of the early Asian (H2N2) isolate A/RI/5+/57, and the results of antigenic and sequence analysis of X-7(F1) and of variants selected with monoclonal antibodies have been combined with a similar analysis of the A/Tokyo/3/67 NA (H2N2, M. R. Lentz, G. M. Air, W. G. Laver, and R. G. Webster (1984), Virology 135, 257-265) to obtain a model of antibody binding to N2 NAs. The selection process was biased, however, since only those monoclonal antibodies which inhibited NA activity could be used to select variants. Most of the changes in the variants selected with monoclonal antibodies occur in those parts of the polypeptide chain which encircle the enzyme active site pocket in the three-dimensional structure (P. M. Colman, J. N. Varghese, and W. G. Laver (1983), Nature (London) 303, 41-44). The results suggest that in general the antibody binds to a site on the NA which includes those amino acid side chains which are altered in monoclonal variants. There are, however, several aspects of the antigen-antibody interaction which are not easily explained, and which will probably only be fully elucidated by X-ray crystallographic analysis of NA-antibody complexes.
G M
GM
Air
M C
MC
Els
L E
LE
Brown
W G
WG
Laver
R G
RG
Webster
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002642:Chick Embryo; D000939:Epitopes / Q000032:analysis*; D005796:Genes; D005814:Genes, Viral; D014644:Genetic Variation; D009980:Influenza A virus / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D009439:Neuraminidase / Q000235:genetics* / Q000276:immunology; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009439:Neuraminidase