Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

Abstract

The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.

Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013–14: Results from the InNHOVE network

“…11 For A (H3N2), while the French national laboratory reported no significant mutation, 12 the region of Navarra, Spain, reported some genetic differences between the circulating and vaccine viruses. 13 14 The L157 mutation observed as part of the virological surveillance scheme, if present in the patients included in the study and if affecting antigenicity, could partially explain the moderate IVE against A(H3N2) we observed this season. A representative virus characterization from the patients included in the various study sites of our multicenter study would be of great value to better interpret vaccines performances against given subtypes as well as IVE differences between study sites.…”

Interim estimates of 2013/14 vaccine effectiveness against influenza A(H1N1)pdm09 from Canada’s sentinel surveillance network, January 2014

“…Other than S185T, present in all 76 sequences, A186T, present in the single Quebec sequence, and possibly N156K and S157L [22], each present in a single and different Alberta sequence, none of the other substitutions were located within or adjacent to the receptor-binding site. With the exception of the single Quebec sequence, antigenic site mutations R205K, A141T, and A186T, which are located close to the receptor-binding site [22][23][24][25] and which occurred in 37%, 30% and 14%, respectively, of sentinel sequences during the 2012/13 season [21], were not evident in 2013/14.…”

Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site

“…Haemagglutination inhibition (HI) assays were carried out as described previously [41,42] Haemagglutination assay with modified turkey erythrocytes Sialic acids were removed from turkey erythrocytes by incubation with Vibrio cholerae NA (VCNA; Roche) as described previously [43]. In brief, a suspension of 1 % turkey erythrocytes in PBS was incubated at 37 C for 1 h with 50 mU VCNA (1 mU µl À1 ) and 10 µl of 0.1 M CaCl 2 .…”