The influenza A virus hemagglutinin glycosylation state affects receptor-binding specificity.

In this study we evaluated the receptor-binding properties of recombinant soluble hemagglutinin (HA) trimers (subtype H2 and H7) produced in insect S2 cells, human HEK293T or HEK293S GnTI(-) cells, which produce proteins with paucimannose, complex or high-mannose N-linked glycans, respectively. The results show that HA proteins that only differ in their glycosylation status possess different receptor fine specificities. HEK293T cell-produced HA displayed a very narrow receptor specificity. However, when treated with neuraminidase this HA was able to bind more glycans with similar specificity as HEK293S GnTI(-) cell-produced HA. Insect cell-produced HA demonstrated decreased receptor specificity. As a consequence, differences in HA fine receptor specificities could not be observed with the insect cell-, but were readily detected with the HEK293S GnTI(-) cell-produced HAs.