A Novel Carbohydrate Addition Site on the Hemagglutinin Protein of a Highly Pathogenic H7 Subtype Avian Influenza Virus

Abstract

The highly pathogenic (HP) avian influenza isolate, A/Fowl/Victoria/76 (H7N7), contains two naturally occurring hemagglutinin (HA) variants. The two hemagglutinin proteins differ only in the possession of a potential asparagine-linked glycosylation site at amino acid position 188-190, which is near the proposed receptor binding region of the HA. Expanded virus plaques which possess the addition site exhibit more slowly migrating HA1 subunits and are significantly more lethal in chickens than those which lack the site. When artificial mixtures of the two variants were inoculated in birds, as few as 1 in 1000 particles containing the glycosylation site was sufficient to exhibit 100% lethality in birds. The data raise the possibility that presence of carbohydrate near the receptor site on the H7 avian influenza virus hemagglutinin may influence virulence.

Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets

“…We speculate the glycosylation may improve virus receptor binding and infectivity in eggs based on similar findings reported for the HPAI virus A/Netherlands/219/2003 (H7N7) in which glycosylation at N133 increased its binding affinity to avian-type ␣2,3-linked sialosides (45). It was also reported that glycosylation at HA position 188 (H3# position 197) near the receptor binding site increased the virulence of an avian H7N7 strain in chicken (46). In contrast, the loss of a glycosylation site at HA position 133 of human H3N2 viruses is associated with better viral growth in MDCK cells (47).…”

Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome

“…Mutations in HA and NA may be important also, because these genes are determinants of the host range of AIV. The addition of a potential N-linked glycosylation site at position 141 in HA may be of importance because changes near the receptor-binding site or at the tip of HA have been implicated in determining the pathogenic properties of H7N7 AIV (31,32).…”

Interdependence of Hemagglutinin Glycosylation and Neuraminidase as Regulators of Influenza Virus Growth: a Study by Reverse Genetics

“…Steric hindrance by a glycan adjacent to the receptorbinding site may therefore be a determinant of receptor specificity. Finally, the number and structure of N-glycans neighboring the receptor-binding pocket have been suggested to determine the host range and pathogenicity of influenza viruses (6,10,29). In view of these findings, it will now be interesting to employ our panel of recombinant viruses to elucidate the contributions of individual HA tip glycans to tissue tropism and host range.…”