title: Role of host-specific amino acids in the pathogenicity of avian H5N1 influenza viruses in mice.
abstract: Recent large-scale sequence analyses revealed 'signature' amino acids at specific positions in viral proteins that distinguish human influenza viruses from avian viruses. To determine the role of these host lineage-specific amino acids in the pathogenicity of H5N1 avian influenza viruses, we generated mutant viruses possessing signature amino acids in the PB2, PA and NP proteins of human influenza isolates ('human-like amino acids') in the genetic background of an avian H5N1 virus, and tested their pathogenicity in mice. We found that some of these mutants exhibited enhanced pathogenicity in mice, suggesting the involvement of these host lineage-specific amino acids in the pathogenicity of H5N1 avian influenza viruses in mammals.
authors.affiliation: Influenza Research Institute, Department of Pathological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000596:Amino Acids / Q000032:analysis*; D000818:Animals; D001921:Brain / Q000821:virology; D002460:Cell Line; D004285:Dogs; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000472:pathogenicity*; D007928:Lethal Dose 50; D008168:Lung / Q000821:virology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009296:Nasal Cavity / Q000821:virology; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000821:virology*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry / Q000235:genetics; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics; D014774:Virulence
chemical_list: D000596:Amino Acids; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; C061290:PA protein, influenza viruses; C057027:PB2 protein, Influenzavirus A; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase