title: Survival analysis of infected mice reveals pathogenic variations in the genome of avian H1N1 viruses.
abstract: Most influenza pandemics have been caused by H1N1 viruses of purely or partially avian origin. Here, using Cox proportional hazard model, we attempt to identify the genetic variations in the whole genome of wild-type North American avian H1N1 influenza A viruses that are associated with their virulence in mice by residue variations, host origins of virus (Anseriformes-ducks or Charadriiformes-shorebirds), and host-residue interactions. In addition, through structural modeling, we predicted that several polymorphic sites associated with pathogenicity were located in structurally important sites, especially in the polymerase complex and NS genes. Our study introduces a new approach to identify pathogenic variations in wild-type viruses circulating in the natural reservoirs and ultimately to understand their infectious risks to humans as part of risk assessment efforts towards the emergence of future pandemic strains.
authors.affiliation: Department of Infectious Diseases, Division of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Zeynep A
authors.initials: ZA
authors.lastname: Koçer
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Huether
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: John
authors.initials: J
authors.lastname: Obenauer
authors.affiliation: Department of Infectious Diseases, Division of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Division of Virology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D000818:Animals; D046091:Charadriiformes / Q000821:virology; D002642:Chick Embryo; D004197:Disease Reservoirs / Q000821:virology; D004372:Ducks / Q000821:virology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D005585:Influenza in Birds / Q000401:mortality / Q000821:virology*; D008811:Mice, Inbred DBA; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D020543:Proteome / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence
chemical_list: D020543:Proteome; D014764:Viral Proteins