title: Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice.
abstract: We examined the molecular basis of virulence of pandemic H1N1/09 influenza viruses by reverse genetics based on two H1N1/09 virus isolates (A/California/04/2009 [CA04] and A/swine/Shandong/731/2009 [SD731]) with contrasting pathogenicities in mice. We found that four amino acid mutations (P224S in the PA protein [PA-P224S], PB2-T588I, NA-V106I, and NS1-I123V) contributed to the lethal phenotype of SD731. In particular, the PA-P224S mutation when combined with PA-A70V in CA04 drastically reduced the virus's 50% mouse lethal dose (LD50), by almost 1,000-fold.
authors: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors: Yipeng
authors: Y
authors: Sun
authors: Qi
authors: Q
authors: Xu
authors: Ye
authors: Y
authors: Shen
authors: Linqing
authors: L
authors: Liu
authors: Kai
authors: K
authors: Wei
authors: Honglei
authors: H
authors: Sun
authors: Juan
authors: J
authors: Pu
authors: Kin-Chow
authors: KC
authors: Chang
authors: Jinhua
authors: J
authors: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009656:North America / Q000453:epidemiology; D009976:Orthomyxoviridae Infections / Q000662:veterinary* / Q000821:virology; D058873:Pandemics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics* / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
chemical_list: C061290:PA protein, influenza viruses; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase