title: Persistent host markers in pandemic and H5N1 influenza viruses.
abstract: Avian influenza viruses have adapted to human hosts, causing pandemics in humans. The key host-specific amino acid mutations required for an avian influenza virus to function in humans are unknown. Through multiple-sequence alignment and statistical testing of each aligned amino acid, we identified markers that discriminate human influenza viruses from avian influenza viruses. We applied strict thresholds to select only markers which are highly preserved in human influenza virus isolates over time. We found that a subset of these persistent host markers exist in all human pandemic influenza virus sequences from 1918, 1957, and 1968, while others are acquired as the virus becomes a seasonal influenza virus. We also show that human H5N1 influenza viruses are significantly more likely to contain the amino acid predominant in human strains for a few persistent host markers than avian H5N1 influenza viruses. This sporadic enrichment of amino acids present in human-hosted viruses may indicate that some H5N1 viruses have made modest adaptations to their new hosts in the recent past. The markers reported here should be useful in monitoring potential pandemic influenza viruses.
authors.affiliation: Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, and Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38105-2794, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Finkelstein
authors.forename: Suraj
authors.initials: S
authors.lastname: Mukatira
authors.forename: Perdeep K
authors.initials: PK
authors.lastname: Mehta
authors.forename: John C
authors.initials: JC
authors.lastname: Obenauer
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Su
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.forename: Clayton W
authors.initials: CW
authors.lastname: Naeve
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001717:Birds / Q000821:virology*; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005819:Genetic Markers; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000302:isolation & purification; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D016296:Mutagenesis; D012621:Seasons; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017423:Sequence Analysis, RNA; D014764:Viral Proteins / Q000235:genetics
chemical_list: D005819:Genetic Markers; D014764:Viral Proteins