Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity

Abstract

The haemagglutinin (HA) glycoproteins of influenza virus membranes are responsible for binding viruses to cells by interacting with membrane receptor molecules which contain sialic acid (for review see ref. 1). This interaction is known to vary in detailed specificity for different influenza viruses (see, for example, refs 2-4) and we have attempted to identify the sialic acid binding site of the haemagglutinin by comparing the amino acid sequences of haemagglutinins with different binding specificities. We present here evidence that haemagglutinins which differ in recognizing either NeuAc alpha 2 leads to 3Gal- or NeuAc alpha 2 leads to 6Gal- linkages in glycoproteins also differ at amino acid 226 of HA1. This residue is located in a pocket on the distal tip of the molecule, an area previously proposed from considerations of the three-dimensional structure of the haemagglutinin to be involved in receptor binding.

Studies on the binding of bacteria to glycolipids Two species of Propionibacterium apparently recognize separate epitopes on lactose of lactosylceramide

“…The situation may therefore be analogous to the receptorbinding variants of influenza virus, which recognize NeuAm2-+3 and NeuAccr2-6, respectively, as a consequence of a single amino acid substitution in the binding site of the hemagglutinin [28].…”

Sequence analysis of the haemagglutinin (HA) of influenza A (H1N1) viruses present in clinical material and comparison with the HA of laboratory-derived virus

“…2), and has also been shown to alter receptor binding in the H1 subtype (Nobusawa & Nakajima, 1988) and receptor specificity in the H3 subtype (Rogers et al, 1983).…”

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

“…The high molecular-weight glycoprotein ␣2-macroglobulin is the major inhibitor in horse, guinea pig and pig sera and equine ␣2-macroglobulin has been particularly well characterized (14,36,37). Resistance to equine ␣2-macroglobulin is associated with a single amino acid alteration at position 226 in the receptor binding pocket of HA and is associated with a change in receptor specificity from sialic acid (SA) linked to galactose by ␣2,6 linkages (SA␣2,6Gal) to SA␣2,3Gal (38,39). We found wild-type HKx31 and a horse serum-resistant mutant of this virus to be equally sensitive to inhibition by murine or human PTX3 (data not shown), indicating definitive differences in mode of action between equine ␣2-macroglobulin and PTX3.…”