title: Two amino acid substitutions in the haemagglutinin of the 2009 pandemic H1N1 virus decrease direct-contact transmission in guinea pigs.
abstract: The 2009 pandemic H1N1 influenza A virus spread across the globe and caused the first influenza pandemic of the 21st century. Many of the molecular factors that contributed to the airborne transmission of this pandemic virus have been determined; however, the direct-contact transmission of this virus remains poorly understood. In this study, we report that a combination of two mutations (N159D and Q226R) in the haemagglutinin (HA) protein of the representative 2009 H1N1 influenza virus A/California/04/2009 (CA04) caused a switch in receptor binding preference from the α2,6-sialoglycan to the α2,3-sialoglycan receptor, and decreased the binding intensities for both glycans. In conjunction with a significantly decreased replication efficiency in the nasal epithelium, this limited human receptor binding affinity resulted in inefficient direct-contact transmission of CA04 between guinea pigs. Our findings highlight the role of the HA gene in the transmission of the influenza virus.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: He
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Kaijun
authors.initials: K
authors.lastname: Jiang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Duan
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Haixu
authors.initials: H
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China.
authors.forename: Xiufan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006168:Guinea Pigs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D011485:Protein Binding; D011956:Receptors, Cell Surface; D053586:Virus Internalization
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011956:Receptors, Cell Surface