title: The special neuraminidase stalk-motif responsible for increased virulence and pathogenesis of H5N1 influenza A virus.
abstract: The variation of highly pathogenic avian influenza H5N1 virus results in gradually increased virulence in poultry, and human cases continue to accumulate. The neuraminidase (NA) stalk region of influenza virus varies considerably and may associate with its virulence. The NA stalk region of all N1 subtype influenza A viruses can be divided into six different stalk-motifs, H5N1/2004-like (NA-wt), WSN-like, H5N1/97-like, PR/8-like, H7N1/99-like and H5N1/96-like. The NA-wt is a special NA stalk-motif which was first observed in H5N1 influenza virus in 2000, with a 20-amino acid deletion in the 49(th) to 68(th) positions of the stalk region. Here we show that there is a gradual increase of the special NA stalk-motif in H5N1 isolates from 2000 to 2007, and notably, the special stalk-motif is observed in all 173 H5N1 human isolates from 2004 to 2007. The recombinant H5N1 virus with the special stalk-motif possesses the highest virulence and pathogenicity in chicken and mice, while the recombinant viruses with the other stalk-motifs display attenuated phenotype. This indicates that the special stalk-motif has contributed to the high virulence and pathogenicity of H5N1 isolates since 2000. The gradually increasing emergence of the special NA stalk-motif in H5N1 isolates, especially in human isolates, deserves attention by all.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, the People's Republic of China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Yu
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Jiagang
authors.initials: J
authors.lastname: Tu
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Yaping
authors.initials: Y
authors.lastname: Peng
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhu
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Li
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
authors.forename: Ziniu
authors.initials: Z
authors.lastname: Yu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ye
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000737:chemistry / Q000502:physiology*; D010948:Viral Plaque Assay; D014774:Virulence
chemical_list: D009439:Neuraminidase