Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957

Abstract

The viruses that caused the three influenza pandemics of the twentieth century in 1918, 1957, and 1968 had distinct hemagglutinin receptor binding glycoproteins that had evolved the capacity to recognize human cell receptors. We have determined the structure of the H2 hemagglutinin from the second pandemic, the ''Asian Influenza'' of 1957. We compare it with the 1918 ''Spanish Influenza'' hemagglutinin, H1, and the 1968 ''Hong Kong Influenza'' hemagglutinin, H3, and show that despite its close overall structural similarity to H1, and its more distant relationship to H3, the H2 receptor binding site is closely related to that of H3 hemagglutinin. By analyzing hemagglutinins of potential H2 avian precursors of the pandemic virus, we show that the human receptor can be bound by avian hemagglutinins that lack the humanspecific mutations of H2 and H3 pandemic viruses, Gln-226Leu, and Gly-228Ser. We show how Gln-226 in the avian H2 receptor binding site, together with Asn-186, form hydrogen bond networks through bound water molecules to mediate binding to human receptor. We show that the human receptor adopts a very similar conformation in both human and avian hemagglutinin-receptor complexes. We also show that Leu-226 in the receptor binding site of human virus hemagglutinins creates a hydrophobic environment near the Sia-1-Gal-2 glycosidic linkage that favors binding of the human receptor and is unfavorable for avian receptor binding. We consider the significance for the development of pandemics, of the existence of avian viruses that can bind to both avian and human receptors.

Structure and Receptor Complexes of the Hemagglutinin from a Highly Pathogenic H7N7 Influenza Virus

“…In addition, two NL219 HA structures, complexed with an avian or human receptor analog (3=SLN or 6=SLN, respectively) were determined, both to a 2.8-Å resolution ( Table 1). The overall structure is similar to those of previously reported HAs, with a globular head containing the receptor binding site and a vestigial esterase domain, and a membrane-proximal domain with its distinctive, central helical stalk, and HA1/HA2 cleavage site (21,22,28,39,41,44,45,55,57,58). Six asparagine-linked glycosylation sites are predicted in the NL219 HA monomer but interpretable carbohydrate electron density was observed only at four sites: Asn28, Asn123, and Asn231 in HA1 and Asn82 in HA2 (Fig.…”

“…The Gal-2 also remains in very close proximity to its counterpart in other structural complexes. The NL219 and all previously reported complexes with ␣2-3 linked analogs revealed no hydrogen bonding between the HA and GlcNAc-3, which suggests that for ␣2-3 linkage glycans, only the first two saccharides are required for HAs to bind to avian receptors (19,22,28,58).…”

A gel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses

“…The determinants of receptor selectivity of many influenza A virus HAs have been extensively characterized by crystallographic analysis of receptor-HA complexes (Skehel and Wiley, 2000;Ha et al, 2001;Gamblin et al, 2004;Stevens et al, 2004Stevens et al, , 2006bLiu et al, 2009). However, there are far fewer studies of the receptor selectivity determinants of influenza B virus HA (Suzuki et al, 1992;Matrosovich et al, 1993;Gambaryan et al, 1997Gambaryan et al, , 1999Wang et al, 2007).…”

Influenza virus surveillance using surface plasmon resonance

“…This binding is essential for the infection, transmission and virulence of influenza viruses. 7,8 The crystal structures of H1, H2, H3, H5, H7 and H9 HA subtypes and their complexes with a2-3 Sia and/or a2-6 Sia glycans have been reported, [9][10][11][12][13][14][15][16] revealing specific interactions between HA and a2-3 Sia or a2-6 Sia glycans. HAs derived from avian influenza viruses bind specifically to the a2-3 Sia glycan, which is preferentially expressed in the intestinal tracts of waterfowl.…”