title: Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction.
abstract: Genetic drift of influenza virus genomic sequences occurs through the combined effects of sequence alterations introduced by a low-fidelity polymerase and the varying selective pressures experienced as the virus migrates through different host environments. While traditional phylogenetic analysis is useful in tracking the evolutionary heritage of these viruses, the specific genetic determinants that dictate important phenotypic characteristics are often difficult to discern within the complex genetic background arising through evolution. Here we describe a novel influenza virus sequence feature variant type (Flu-SFVT) approach, made available through the public Influenza Research Database resource (www.fludb.org), in which variant types (VTs) identified in defined influenza virus protein sequence features (SFs) are used for genotype-phenotype association studies. Since SFs have been defined for all influenza virus proteins based on known structural, functional, and immune epitope recognition properties, the Flu-SFVT approach allows the rapid identification of the molecular genetic determinants of important influenza virus characteristics and their connection to underlying biological functions. We demonstrate the use of the SFVT approach to obtain statistical evidence for effects of NS1 protein sequence variations in dictating influenza virus host range restriction.
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jyothi M
authors.initials: JM
authors.lastname: Noronha
authors.forename: Mengya
authors.initials: M
authors.lastname: Liu
authors.forename: R Burke
authors.initials: RB
authors.lastname: Squires
authors.forename: Brett E
authors.initials: BE
authors.lastname: Pickett
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hale
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Air
authors.forename: Summer E
authors.initials: SE
authors.lastname: Galloway
authors.forename: Toru
authors.initials: T
authors.lastname: Takimoto
authors.forename: Mirco
authors.initials: M
authors.lastname: Schmolke
authors.forename: Victoria
authors.initials: V
authors.lastname: Hunt
authors.forename: Edward
authors.initials: E
authors.lastname: Klem
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Monnie
authors.initials: M
authors.lastname: McGee
authors.forename: Richard H
authors.initials: RH
authors.lastname: Scheuermann
mesh_terms: D000595:Amino Acid Sequence; D014644:Genetic Variation; D058507:Host Specificity; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000502:physiology; D007251:Influenza, Human / Q000821:virology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins