Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X

Abstract

Influenza viruses isolated from ducks are rarely able to infect chickens; it is therefore postulated that these viruses need to adapt in some way to be able to transmit to chickens in nature. Previous studies revealed that sialyl Lewis X (3′SLeX), which is fucosylated α2,3 sialoside was predominantly detected on the epithelial cells of the chicken trachea, whereas this glycan structure is not found in the duck intestinal tract. To clarify the mechanisms of the interspecies transmission of influenza viruses between ducks and chickens, we compared the receptor specificity of low pathogenic avian influenza viruses isolated from these two species. Glycan-binding analysis of the recombinant hemagglutinin (HA) of a chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2), revealed a binding preference to α1,3 fucosylated sialosides. On the other hand, the HA of a duck influenza virus, A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG), particularly bound to non-fucosylated α2,3 sialosides such as 3-sialyllactosamine (3′SLacNAc). Computational analyses along with binding analyses of the mutant HAs revealed that this glycan-binding specificity of the HA was determined by amino acid residues at positions 222 and 227. Inconsistent with the glycan-binding specificity of the recombinant HA protein, virions of Dk/MNG bound to both 3′SLacNAc and 3′SLeX. Glycan-binding analysis in the presence of a neuraminidase (NA) inhibitor revealed that the NA conferred binding to 3′SLeX to virions of Dk/MNG. The present results reveal the molecular basis of the interaction between fucosylated α2,3 sialosides and influenza viruses.

Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016

“…Our isolates have the amino acid sequence QQG at positions 226–228, which are located at the receptor-binding site in the HA protein, although the corresponding amino acid sequences of the previous H5 viruses are QSG or QRG (Technical Appendix Figure 2). These findings suggest that the receptor specificity of our H5N6 HPAIV isolates might be altered from their parental viruses ( 12 , 13 ). We also found 11 aa deletions in the stalk region of the NA protein, unlike that of A/duck/Vietnam/HU1–1151/2014 (H5N6), a representative virus strain of an N6 NA gene-based group D (Technical Appendix Figure 3), which belongs to a different cluster of the clade 2.3.4.4.…”

Comparative pathogenicity of H5N6 subtype highly pathogenic avian influenza viruses in chicken, Pekin duck and Muscovy duck

“…However, the viruses replicated effectively in all three hosts and no statistically significant difference was seen when the maximum viral titres in swabs from each host were compared. The amino acids at positions 222 and 227 are involved in receptor‐binding preferences in avian species (Hiono et al., , ). Some H5 HPAIVs possessing R/Q and R at positions 222 and 227 respectively, in HA bind to fucosylated α2,3 sialoside in their hosts, which is expressed on the epithelial cells of chicken trachea but is not found in the duck intestinal tract.…”

Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild and captive birds in the winter season of 2016–2017 in Northern Japan

“…One previous study's findings indicated that recent H5Nx viruses exhibited alterations in their receptor binding specificity compared with previous HPAIVs , these viruses preferring fucosylated α2,3 sialosides in addition to typical non‐fucosylated α2,3 sialosides. Fucosylation of α2,3 sialosides is thought to be a molecular determinant of host preferences by avian influenza viruses in ducks and chickens in that chicken viruses prefer fucosylated α2,3 sialosides whereas duck viruses prefer non‐fucosylated α2,3 sialosides . All the viruses isolated in the present study possess a glutamine at position 222 of the HA, which is a key amino acid residue for the recognition of fucosylated α2,3 sialosides.…”