Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4

• Published in: Cell reports (Cambridge) Vol. 20; no. 5; pp. 1201 - 1214
• Main Authors: Song, Hao, Qi, Jianxun, Xiao, Haixia, Bi, Yuhai, Zhang, Wei, Xu, Ying, Wang, Fei, Shi, Yi, Gao, George F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2017; Elsevier
• Subjects: Amino Acid Substitution; crystal structure; H4 hemagglutinin; H4N6; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; host jump; Humans; Influenza A virus - chemistry; Influenza A virus - genetics; Influenza A virus - metabolism; influenza virus; Mutation, Missense; receptor binding; transmission; H4 hemagglutinin; transmission; host jump; H4N6; influenza virus; receptor binding; crystal structure
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.07.028

Low-pathogenicity avian influenza viruses (LPAIVs) have caused a global concern to public health since the first novel LPAIV H7N9 outbreak occurred. The receptor-binding properties of the viral hemagglutinin are one key factor for efficient transmission and infection in humans. Recent evidence shows that H4 subtype viruses have been widely circulating in domestic poultry and human asymptomatic infections might have occurred. Here, we evaluated the receptor-binding properties of two representative isolates, avian H4N6 (containing Q226 and G228) and swine H4N6 (containing L226 and S228), and found that the avian isolate preferentially binds to avian receptors, whereas the swine isolate preferentially binds to human receptors. The Q226L and G228S substitutions are pivotal for the receptor-binding switch, which resulted in similar human receptor-binding features to the pandemic H2 and H3, implying that H4 has the potential to cause human infections. This early-warning study calls for future extensive surveillance. [Display omitted] •Structures of H4 hemagglutinin and its complex with avian or human receptor analogs•The substitutions in Q226L and G228S switch specificity from avian to human receptor binding•Structural basis for the switch from avian to human receptor binding by H4•H4 virus has the potential to cause human pandemics The shift in the receptor-binding specificity of avian influenza virus is critical for the jump from avian to human hosts. Based on receptor-binding analysis and structural studies, Song et al. report the mechanisms behind the avian-to-human receptor-binding adaptation by influenza A virus hemagglutinin H4.