title: Mutations in PA, NP, and HA of a pandemic (H1N1) 2009 influenza virus contribute to its adaptation to mice.
abstract: In 2009, a swine-origin H1N1 influenza virus caused the first pandemic of the 21st century. To understand the molecular basis of pandemic influenza virus adaptation to new host species, we serially passaged the pandemic (H1N1) 2009 virus strain A/California/04/09 in mouse lungs. After ten passages, the virus became lethal to mice. We found eight amino acid differences between the wild-type and mouse-adapted viruses: one in PB1, three in PA, three in HA, and one in NP. By using reverse genetics to generate mutant viruses, we determined that the amino acid substitutions in PA (at positions 21 and 616), HA (at positions 127 and 222), and NP (at position 375) play independent roles in the increased pathogenicity in mice. Among these five substitutions, an aspartic acid-to-glutamic acid substitution at position 127 in HA contributed to efficient viral replication in mouse lungs. Our results suggest the importance of the viral polymerase complex and of HA in viral adaption to a new host.
authors: Division of Virology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors: Saori
authors: S
authors: Sakabe
authors: Makoto
authors: M
authors: Ozawa
authors: Ryo
authors: R
authors: Takano
authors: Kiyoko
authors: K
authors: Iwastuki-Horimoto
authors: Yoshihiro
authors: Y
authors: Kawaoka
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D004252:DNA Mutational Analysis; D005260:Female; D006389:Hemagglutinins, Viral / Q000235:genetics*; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D019590:Nucleocapsid Proteins; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D006389:Hemagglutinins, Viral; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; C061290:PA protein, influenza viruses; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; C458881:hemagglutinin fusogenic peptide, influenza virus; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase