title: Structural and Functional Studies of Influenza Virus A/H6 Hemagglutinin.
abstract: In June 2013, the first human infection by avian influenza A(H6N1) virus was reported in Taiwan. This incident raised the concern for possible human epidemics and pandemics from H6 viruses. In this study, we performed structural and functional investigation on the hemagglutinin (HA) proteins of the human-infecting A/Taiwan/2/2013(H6N1) (TW H6) virus and an avian A/chicken/Guangdong/S1311/2010(H6N6) (GD H6) virus that transmitted efficiently in guinea pigs. Our results revealed that in the presence of HA1 Q226, the triad of HA1 S137, E190 and G228 in GD H6 HA allows the binding to both avian- and human-like receptors with a slight preference for avian receptors. Its conservation among the majority of H6 HAs provides an explanation for the broader host range of this subtype. Furthermore, the triad of N137, V190 and S228 in TW H6 HA may alleviate the requirement for a hydrophobic residue at HA1 226 of H2 and H3 HAs when binding to human-like receptors. Consequently, TW H6 HA has a slight preference for human receptors, thus may represent an intermediate towards a complete human adaptation. Importantly, the triad observed in TW H6 HA is detected in 74% H6 viruses isolated from Taiwan in the past 14 years, suggesting an elevated threat of H6 viruses from this region to human health. The novel roles of the triad at HA1 137, 190 and 228 of H6 HA in binding to receptors revealed here may also be used by other HA subtypes to achieve human adaptation, which needs to be further tested in laboratory and closely monitored in field surveillance.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Ni
authors.affiliation: Life Sciences Collaborative Access Team (LS-CAT), Synchrotron Research Center, Northwestern University, Argonne, Illinois, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Kondrashkina
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D002645:Chickens / Q000821:virology; D006168:Guinea Pigs; D006389:Hemagglutinins, Viral / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000302:isolation & purification / Q000502:physiology / Q000648:ultrastructure*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D009976:Orthomyxoviridae Infections / Q000821:virology; D010802:Phylogeny; D011487:Protein Conformation
chemical_list: D006389:Hemagglutinins, Viral