Receptor binding by an H7N9 influenza virus from humans

Abstract

Of the 132 people known to have been infected with H7N9 influenza viruses in China, 37 died, and many were severely ill. Infection seems to have involved contact with infected poultry. We have examined the receptor-binding properties of this H7N9 virus and compared them with those of an avian H7N3 virus. We find that the human H7 virus has significantly higher affinity for α-2,6-linked sialic acid analogues ('human receptor') than avian H7 while retaining the strong binding to α-2,3-linked sialic acid analogues ('avian receptor') characteristic of avian viruses. The human H7 virus does not, therefore, have the preference for human versus avian receptors characteristic of pandemic viruses. X-ray crystallography of the receptor-binding protein, haemagglutinin (HA), in complex with receptor analogues indicates that both human and avian receptors adopt different conformations when bound to human H7 HA than they do when bound to avian H7 HA. Human receptor bound to human H7 HA exits the binding site in a different direction to that seen in complexes formed by HAs from pandemic viruses and from an aerosol-transmissible H5 mutant. The human-receptor-binding properties of human H7 probably arise from the introduction of two bulky hydrophobic residues by the substitutions Gln226Leu and Gly186Val. The former is shared with the 1957 H2 and 1968 H3 pandemic viruses and with the aerosol-transmissible H5 mutant. We conclude that the human H7 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses, but its retained preference for avian receptor may restrict its further evolution towards a virus that could transmit efficiently between humans, perhaps by binding to avian-receptor-rich mucins in the human respiratory tract rather than to cellular receptors.

Structural basis for preferential avian receptor binding by the human-infecting H10N8 avian influenza virus

“…23). The different outcomes could be due to the different receptor-binding properties of the H5N1 and H7N9 viruses 15,[24][25][26][27][28][29][30][31][32] . The H5N1 viruses display strong binding to avian receptors and weak binding to human receptors, and sporadically infect humans.…”

Prevention of influenza by targeting host receptors using engineered proteins

“…Human influenza viruses such as the 2009 pandemic H1N1 virus recognize α-2,6-linked sialic acid receptors present in the upper respiratory tract, whereas avian influenza viruses such as H5N1 predominantly recognize α-2,3-linked sialic acid receptors, which are present in the human lower respiratory tract as well (12,13). The recently emerged human H7N9 influenza virus is unusual in recognizing both types of receptors and therefore has the possibility of sustained human-to-human transmission and pandemic potential (14,15).…”

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

“…13 N9-NA also demonstrates receptor binding properties with a preference to binding human α-2,6 linkages. 14 Of note, before the fifth outbreak, human infections were caused by a low pathogenic avian influenza, which caused little or no disease in infected poultry. 6 However, in February of 2017 the National Health and Family Planning Commission of China reported genetic sequences from virus isolates from two patients located in Guangdong Province that had insertions at the HA gene cleavage site which is suggestive of a highly pathogenic avian influenza.…”