title: [Antigenic structure of influenza A virus subtype H5 hemagglutinin: mechanism of acquiring stability to monoclonal antibodies in escape-mutants].
abstract: The analysis of escape mutants of the avian influenza virus of H5 subtype (strain A/Mallard/Pennsylvania/10218/84) revealed the location and structure of two antigenic sites in the hemagglutinin (HA) molecule. Several escape mutants exhibited unusual features in the reactions with monoclonal antibodies (Mabs), being completely resistant in the infectivity neutralization test to the Mabs used for their selection, and retaining the ability to bind the Mabs as revealed by enzyme-linked immunosorbent assay. An enhancement of the binding by an amino acid change in a different antigenic site was demonstrated, as well as a complete abolishment of the binding by a mutation selected by passage in the presence of an excess of the non-neutralizing Mab of high binding ability. The observed effects did not result from the changes in the affinity of the mutant HA toward sialic receptors. The data suggest that one amino acid change in HA may prevent the virus neutralization by different mechanisms for different Mabs: either the binding of the Mab to HA is prevented, or the bound Mab is unable to block the receptor-binding pocket of HA. Different mechanisms of the acquisition of resistance to Mabs in the course of the selection of escape mutants are discussed.
authors.affiliation: Ivanovsky's Research Institute for Virology, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: N A
authors.initials: NA
authors.lastname: Il'iushina
authors.forename: I A
authors.initials: IA
authors.lastname: Rudneva
authors.forename: N L
authors.initials: NL
authors.lastname: Varich
authors.forename: A S
authors.initials: AS
authors.lastname: Lipatov
authors.forename: R G
authors.initials: RG
authors.lastname: Webster
authors.forename: N V
authors.initials: NV
authors.lastname: Kaverin
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D009154:Mutation
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral