Regulation of receptor binding affinity of influenza virus hemagglutinin by its carbohydrate moiety

Abstract

The hemagglutinin (HA) of the fowl plague virus (FPV) strain of influenza A virus has two N-linked oligosaccharides attached to Asn123 and Asn149 in the vicinity of the receptor binding site. The effect of these carbohydrate side chains on the binding of HA to neuraminic acid-containing receptors has been analyzed. When the oligosaccharides were deleted by site-specific mutagenesis, HA expressed from a simian virus 40 vector showed enhanced hemadsorbing activity. Binding was so strong under these conditions that erythrocytes were no longer released by viral neuraminidase and that release was significantly reduced when neuraminidase from Vibrio cholerae was used. Similarly, when these oligosaccharides were removed selectively from purified viruses by N-glycosidase F, such virions were unable to elute from receptors, although they retained neuraminidase activity. Thus, release of FPV from cell receptors depends on the presence of the HA glycans at Asn123 and Asn149. On the other hand, receptor binding was abolished when these oligosaccharides were sialylated after expression in the absence of neuraminidase (M. Ohuchi, A. Feldmann, R. Ohuchi, and H.-D. Klenk, Virology 212:77-83, 1995). These observations indicate that the receptor affinity of FPV HA is controlled by oligosaccharides adjacent to the receptor binding site.

The ecology and adaptive evolution of influenza A interspecies transmission

“…94,98,99 Finally, mutations outside the RBS, specifically in glycosylation sites near the RBS, have also been determinants of receptor binding specificity, as these sites, when glycosylated, cause stearic hindrance to the optimal binding of respective SA linkage to the RBS, thereby restricting binding. [100][101][102][103][104][105] As mentioned earlier, the stability of the HA protein at various pH is associated with transmission in different hosts, with mammalian viruses having a lower optimum pH of conformational stability than avian viruses. 35,[106][107][108] However, it was recently discovered that, in the adaptation from avian H1N1 to establishment of the European avianlike (EA) swine virus lineage, this mammalian virus possessed a higher optimum pH of conformational stability than its avian counterpart, which is hypothesized to be mediated by changes in HA2 residues 72, 75, and 113.…”

Endocytosis of the receptor-binding domain of SARS-CoV spike protein together with virus receptor ACE2

“…Glycosylation on spike proteins has been reported to affect virus entry (Fenouillet et al, 1990;Goffard et al, 2005;Ohuchi et al, 1997). For the influenza virus, certain glycans near the receptorbinding site affect the binding of the HA to cellular receptors (Ohuchi et al, 1997). We therefore explored whether glycosylation on the RBD spike protein has an effect on the interaction between SARS-CoV and ACE2.…”

Adaptation of avian influenza A (H6N1) virus from avian to human receptor‐binding preference

“…To date, 16 functional HA subtypes (H1-H16) and nine functional NA subtypes (N1-N9) have been identified, not including recently identified HA and NA homologues (H17, H18, N10, and N11) from bat-derived influenza-like virus genomes Tong et al, 2012Tong et al, , 2013Zhu et al, 2012Zhu et al, , 2013Sun et al, 2013;Wu et al, 2014). The functional balance between HA and NA activities is important for viral pathogenicity, replication efficiency, and transmissibility (Baum & Paulson, 1991;Ohuchi et al, 1997;Wagner et al, 2000;de Wit et al, 2010).…”