title: Genomic signature and protein sequence analysis of a novel influenza A (H7N9) virus that causes an outbreak in humans in China.
abstract: Very recently, a new avian flu outbreak in humans, which is caused by a novel H7N9 influenza A virus (AIV), was reported in China. As of April 13, 2013, 49 confirmed cases (mainly middle-aged to elderly males), including 11 deaths, were reported in China. Here we analyzed the genomic signatures and protein sequences of the human H7N9 AIVs. We found that the genomic signatures of A(H7N9) had high and low identity to avian and human IAVs, respectively, suggesting its avian origin. The signature amino acids of A(H7N9) had high identity to 1997 H5N1 and 2009 H1N1, but low identity to those influenza strains that caused pandemics before 1980. One of the key signature amino acids at 627 in PB2 mutated to lysine, which is associated with mammalian adaptation and increased virulence of the highly pathogenic avian influenza A(H5N1) virus. Besides, several other human-like signatures, including PB2-44S, PA-100A, PA-356R, and PA-409N are also found in this avian-origin A(H7N9) virus. The HA protein has the Q226L mutation, which is associated with increased binding to mammalian-like receptors bearing alpha 2,6 receptor in the human upper airway. The M2 protein contains the N31S mutation, suggesting its resistance to the M2 channel blockers amantadine and rimantadine. These findings suggest that this avian-origin AIV gains its bird-to-human, i.e., zoonotic, transmissibility and increased virulence, as well as drug-resistance, by mutating key signature amino acid residues and those in the functional domains of the viral proteins. Therefore, it is prudent to monitor the evolution of A(H7N9), as well as develop strategies to combat any potential epidemic or pandemic.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Sun
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Chen
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wen
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D002681:China / Q000453:epidemiology; D004196:Disease Outbreaks; D016679:Genome, Viral; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D007251:Influenza, Human / Q000821:virology*; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins