RESUMO
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.
Assuntos
Evolução Molecular , Genoma Viral , Vírus da Influenza A/genética , Influenza Humana/virologia , Mutagênese/genética , Animais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , História do Século XX , História do Século XXI , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/fisiologia , Vacinas contra Influenza/história , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Influenza Humana/veterinária , Mutação/genética , Neuraminidase/genética , Neuraminidase/metabolismo , New York/epidemiologia , Filogenia , Setor Público , Vírus Reordenados/genética , Análise de Sequência , Fatores de Tempo , Replicação ViralRESUMO
FLAN (short for FLu ANnotation), the NCBI web server for genome annotation of influenza virus (http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/annotation.cgi) is a tool for user-provided influenza A virus or influenza B virus sequences. It can validate and predict protein sequences encoded by an input flu sequence. The input sequence is BLASTed against a database containing influenza sequences to determine the virus type (A or B), segment (1 through 8) and subtype for the hemagglutinin and neuraminidase segments of influenza A virus. For each segment/subtype of the viruses, a set of sample protein sequences is maintained. The input sequence is then aligned against the corresponding protein set with a 'Protein to nucleotide alignment tool' (ProSplign). The translated product from the best alignment to the sample protein sequence is used as the predicted protein encoded by the input sequence. The output can be a feature table that can be used for sequence submission to GenBank (by Sequin or tbl2asn), a GenBank flat file, or the predicted protein sequences in FASTA format. A message showing the length of the input sequence, the predicted virus type, segment and subtype for the hemagglutinin and neuraminidase segments of Influenza A virus will also be displayed.
Assuntos
DNA Viral/análise , Genes Virais , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Internet , Software , Vírus/classificação , Algoritmos , Sequência de Aminoácidos , Gráficos por Computador , Genoma Viral , Genótipo , Vírus da Influenza A/classificação , Vírus da Influenza B/classificação , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
It presents a report in the journal of Nature, of the sequencing of 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides.