Change in Receptor-Binding Specificity of Recent Human Influenza A Viruses (H3N2): A Single Amino Acid Change in Hemagglutinin Altered Its Recognition of Sialyloligosaccharides

Abstract

Human H3N2 influenza A viruses were known to preferentially bind to sialic acid (SA) in alpha2,6Gal linkage on red blood cells (RBC). However, H3N2 viruses isolated in MDCK cells after 1992 did not agglutinate chicken RBC (CRBC). Experiments with point-mutated hemagglutinin (HA) of A/Aichi/51/92, one of these viruses, revealed that an amino acid change from Glu to Asp at position 190 (E190D) was responsible for the loss of ability to bind to CRBC. A/Aichi/51/92 did not agglutinate CRBC treated with alpha2, 3-sialidase, suggesting that SAalpha2,3Gal on CRBC might not inhibit the binding of the virus to SAalpha2,6Gal on CRBC. However, the virus agglutinated derivatized CRBC resialylated with SAalpha2, 6Galbeta1,4GlcNAc. These findings suggested that the E190D change might have rendered the HA able to distinguish sialyloligosaccharides on the derivatized CRBC containing the SAalpha2,6Galbeta1,4GlcNAc sequence from those on the native CRBC.

New reassortant and enzootic European swine influenza viruses transmit efficiently through direct contact in the ferret model

“…These amino acids have previously been shown, for the human H3 subtype, to reduce the affinity for 2,3-a receptor binding, as well as increasing the affinity for 2,6-a receptors (Matrosovich et al, 2000;Nobusawa et al, 2000;Rogers et al, 1983). Taken together, these findings are in accordance with the observed ability of H3N2 to infect both human and swine cell lines, as well as infect and transmit between ferrets.…”

Pattern Recognition Molecule Mindin Promotes Intranasal Clearance of Influenza Viruses

“…HA protein on influenza virus particles binds with sialic acid on the surface of cRBC and agglutinates cRBC (31). As shown in Fig.…”

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

“…Amino acid substitution 150HR in NA was found to be responsible for the agglutination of turkey and human type O erythrocytes and this substitution has recently become dominant in A(H3N2) viruses. Fluctuations of the haemagglutination activity of HA have been observed in the past, due to amino acid changes in the HA of influenza A(H3N2) and A(H1N1) viruses that led to the inability to agglutinate chicken erythrocytes [14][15][16]. Because erythrocytes of different animal species contain different oligosaccharide structures on their surface, changes in the receptor specificity of HA of influenza viruses have been shown to correlate with differences in haemagglutination behaviour [17].…”

“…Changes in HA affinity to erythrocytes from different species have been observed occasionally since influenza A(H3N2) viruses have been circulating in the human population [14][15][16][17]. Since the early 2000s, several groups have observed changes in the haemagglutination behaviour of influenza A(H3N2) viruses, i.e.…”