A highly pathogenic avian influenza subtype H5 virus displays a higher affinity to “human-like” linked sialic acid than “avian-like”

Recent human infections caused by highly pathogenic avian influenza viruses (HPAIV) emphasize an urgent need for the assessment of factors that allow adaptation of avian viruses to humans. We have conducted a comparative study of the hemagglutinin (HA) receptor binding specificity of a number of HPAIV and low pathogenic avian influenza viruses (LPAIV) of H5N1,H5N9, H5N6, H5N2, H7N7 and H9N2 subtypes by testing the direct binding of whole viruses to synthetic analogs of natural influenza virus receptors, biotin-labeled sialylglycoconjugates. This simple and sensitive method allows a quantitative investigation not only of the receptor preferences for alpha2,3- or alpha2,6-linked sialic acid, but also detects fine differences in HA specificity, such as fucosylation or sulfatation of the terminal trisaccharide or carbohydrate core differences. We have identified an avian strain of subtype H5 which showed the same binding to oligosaccharide (OS) with alpha2,6-linked sialic acid (“human-like”-linked) and to OS with alpha2,3-linked sialic acid (“avian-like”-linked). Sequence analysis of the HA gene revealed a mutation S227N in the HA receptor binding site.