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Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction.

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.

Pubmed ID: 22398283

Authors

  • Noronha JM
  • Liu M
  • Squires RB
  • Pickett BE
  • Hale BG
  • Air GM
  • Galloway SE
  • Takimoto T
  • Schmolke M
  • Hunt V
  • Klem E
  • GarcĂ­a-Sastre A
  • McGee M
  • Scheuermann RH

Journal

Journal of virology

Publication Data

May 25, 2012

Associated Grants

  • Agency: Medical Research Council, Id: G0801822
  • Agency: PHS HHS, Id: HHSN266200700010C
  • Agency: NIAID NIH HHS, Id: N01AI400041
  • Agency: NIAID NIH HHS, Id: R01 AI050933

Mesh Terms

  • Amino Acid Sequence
  • Genetic Variation
  • Host Specificity
  • Humans
  • Influenza A virus
  • Influenza, Human
  • Molecular Sequence Data
  • Phylogeny
  • Protein Structure, Secondary
  • Sequence Alignment
  • Viral Nonstructural Proteins