title: The antigenic drift molecular basis of the H5N1 influenza viruses in a novel branch of clade 2.3.4.
abstract: H5N1 subtype influenza A virus has evolved into many HA clades since late 1990 s. Six circulating H5N1 influenza viruses clustered to a novel branch in clade 2.3.4 and could escape vaccine protection, indicating their antigenic drift. Eleven amino acids substitutions in three antigenic sites of the hemagglutinin of these isolates were found when compared with the hemagglutinin of the primary viruses in clade 2.3.4. On the backbone of the novel isolates A/chicken/Northern China/k0602/2010, we generated a panel of recombinant viruses with HA mutations of restoring the primary vaccine strain Re-5's amino acid and homologous antisera to determine the role of these substitutions. The results of cross-HI assay, micro-neutralization assay and the antigen map of the mutated recombinant viruses showed that three substitutions in antigenic site B, especially D205K, are the major contributors to the antigenic drift of the novel branch of clade 2.3.4. Our study highlights the importance of surveillance of antigenic drift of H5N1 viruses for the control and preparedness of pandemic threats.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhong
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Kunkun
authors.initials: K
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Qunhui
authors.initials: Q
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Peng
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-Innovation Center of Jiangsu for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China. Electronic address: xfliu@yzu.edu.cn.
authors.forename: Xiufan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002645:Chickens; D002681:China; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D007106:Immune Sera / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D005585:Influenza in Birds / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007106:Immune Sera; D007252:Influenza Vaccines
keywords: Amino acid position 205; Antigenic drift; Antigenic site B; Clade 2.3.4; H5N1