Scientific Publications by FDA Staff

Virology 2009 Nov 25;394(2):218-26

Changes of the receptor-binding properties of influenza B virus B/Victoria/504/2000 during adaptation in chicken eggs.

Lugovtsev VY, Smith DF, Weir JP

Selection of high-growth virus variants of strain B/Victoria/504/2000 by serial passage in eggs resulted in three amino acid substitutions, G141E, R162M, and D196Y, in the vicinity of the receptor-binding pocket of viral hemagglutinin. Virus variants containing the identified amino acid substitutions, individually or in various combinations, were constructed using reverse genetics and analyzed for their receptor-binding properties using glycan microarray platform. Three different patterns of virus binding were revealed. A low-growth virus variant, corresponding to the original egg-derived virus B/Victoria/504/2000 prior to acquisition of amino acid changes G141E, R162M, and D196Y, had a clear preference for the oligosaccharide chains terminated with alpha2-6-linked sialic acid with very weak binding of the glycans terminated with alpha2-3-linked sialic acid. Amino acid substitutions R162M and D196Y had similar effects, resulting in viruses that bound with high efficiency almost all terminally sialylated glycans represented on the array regardless of the type of glycosidic linkage. In contrast, substitution of G141E alone, or in combinations with the other two amino acid substitutions, significantly restricted virus glycan-binding capabilities. All virus variants possessing this substitution lost the ability to bind glycans with alpha2-6 glycosidic linkage as well as most of the glycans with alpha2-3 glycosidic linkage. Linear penta- and heptasaccharide chains represented at the non-reducing end by alpha2-3 sialylated Type-II motif (LacNAc) were the only structures bound with high affinity by the virus variants with G141E substitution. In all cases when the effects on virus binding of individual amino acid substitutions differed, the effect of R162M was subordinate to the effect of either G141E or D196Y.