title: Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution.
abstract: Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.
authors.affiliation: The Institute for Genomic Research, 9712 Medical Center Dr., Rockville, Maryland 20850, USA.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Sengamalay
authors.forename: Martin
authors.initials: M
authors.lastname: Shumway
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zaborsky
authors.forename: Tamara
authors.initials: T
authors.lastname: Feldblyum
authors.forename: Vik
authors.initials: V
authors.lastname: Subbu
authors.forename: David J
authors.initials: DJ
authors.lastname: Spiro
authors.forename: Jeff
authors.initials: J
authors.lastname: Sitz
authors.forename: Hean
authors.initials: H
authors.lastname: Koo
authors.forename: Pavel
authors.initials: P
authors.lastname: Bolotov
authors.forename: Dmitry
authors.initials: D
authors.lastname: Dernovoy
authors.forename: Tatiana
authors.initials: T
authors.lastname: Tatusova
authors.forename: Yiming
authors.initials: Y
authors.lastname: Bao
authors.forename: Kirsten
authors.initials: K
authors.lastname: St George
authors.forename: Jill
authors.initials: J
authors.lastname: Taylor
authors.forename: David J
authors.initials: DJ
authors.lastname: Lipman
authors.forename: Claire M
authors.initials: CM
authors.lastname: Fraser
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
authors.forename: Steven L
authors.initials: SL
authors.lastname: Salzberg
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D016679:Genome, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D007252:Influenza Vaccines / Q000266:history / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000635:transmission / Q000662:veterinary / Q000821:virology*; D016296:Mutagenesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D009518:New York / Q000453:epidemiology; D010802:Phylogeny; D017150:Public Sector; D016865:Reassortant Viruses / Q000235:genetics; D017421:Sequence Analysis; D013997:Time Factors; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C109963:hemagglutinin, avian influenza A virus; D009439:Neuraminidase