title: Conserved amino acid markers from past influenza pandemic strains.
abstract: BACKGROUND
  Finding the amino acid mutations that affect the severity of influenza infections remains an open and challenging problem. Of special interest is better understanding how current circulating influenza strains could evolve into a new pandemic strain. Influenza proteomes from distinct viral phenotype classes were searched for class specific amino acid mutations conserved in past pandemics, using reverse engineered linear classifiers.
  
  
  RESULTS
  Thirty-four amino acid markers associated with host specificity and high mortality rate were found. Some markers had little impact on distinguishing the functional classes by themselves, however in combination with other mutations they improved class prediction. Pairwise combinations of influenza genomes were checked for reassortment and mutation events needed to acquire the pandemic conserved markers. Evolutionary pathways involving H1N1 human and swine strains mixed with avian strains show the potential to acquire the pandemic markers with a double reassortment and one or two amino acid mutations.
  
  
  CONCLUSIONS
  The small mutation combinations found at multiple protein positions associated with viral phenotype indicate that surveillance tools could monitor genetic variation beyond single point mutations to track influenza strains. Finding that certain strain combinations have the potential to acquire pandemic conserved markers through a limited number of reassortment and mutation events illustrates the potential for reassortment and mutation events to lead to new circulating influenza strains.
authors.affiliation: Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA. allen99@llnl.gov
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Allen
authors.forename: Shea N
authors.initials: SN
authors.lastname: Gardner
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Vitalis
authors.forename: Tom R
authors.initials: TR
authors.lastname: Slezak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds / Q000821:virology; D017124:Conserved Sequence; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005819:Genetic Markers; D016679:Genome, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D009154:Mutation; D040901:Proteomics; D016865:Reassortant Viruses / Q000235:genetics; D016415:Sequence Alignment; D013045:Species Specificity; D013552:Swine; D014764:Viral Proteins / Q000235:genetics
chemical_list: D005819:Genetic Markers; D014764:Viral Proteins