Antigenic drift in type A influenza virus: Peptide mapping and antigenic analysis of A/PR/8/34 (HON1) variants selected with monoclonal antibodies

Abstract

Variants of A/PR/8/34 (HON1) influenza virus, having hemagglutinin molecules with probably a single altered antigenic determinant, were isolated by growing the virus in the presence of the monoclonal hybridoma antibody [Ab] PEG-1. The variants were analyzed by peptide mapping and characterized antigenically by using PEG-1 and 4 other monoclonal hybridoma Ab to PR8 hemagglutinin. Peptide maps of the large hemagglutinin polypeptide HA1 from 8 of 10 variants showed a single changed peptide. This peptide from 2 of the variants was analyzed, and in each case a serine residue in the wild-type hemagglutinin was replaced by leucine in the variant. Although these 8 variants showed identical peptide maps, 1 could be discriminated antigenically from the others with 1 of the hybridomas. (The peptide maps represented about 1/3 of the HA1 molecule.) Of the other 2 variants, 1 gave the same HA1 map as the wild type, but could be distinguished antigenically from wild type virus by 2 of the hybridomas. The other was unique and could be distinguished antigenically and by peptide mapping from the other variants. Since a large number of the variants selected with PEG-1 showed the same peptide change, this alteration in amino acid sequence (serine to leucine) was probably responsible for the inability of the variants to bind PEG-1 monoclonal Ab. The changed amino acids were located within the antigenic sites or the change occurred somewhere else in the hemagglutinin molecule and altered the determinants through conformational changes.