Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution
Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution
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DOI：
10.1038/nature04239
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发表时间：
2005-10-20
期刊：
影响因子：
64.8
通讯作者：
Salzberg, SL
中科院分区：
文献类型：
--
作者：
Ghedin, E;Sengamalay, NA;Salzberg, SL
流感病毒非常善于在人群中长时间存活。人甲型流感病毒甚至在广泛获得疫苗的人群中继续流行，并继续成为发病和死亡的主要原因（1，2）。这种病毒每年都会发生变异，使现有的疫苗定期失效，并需要为新疫苗选择新的毒株。不太频繁的重大变化，称为抗原转移，产生新的菌株，人类对这些菌株几乎没有保护性免疫力，从而导致世界范围的流行病。最近的流行病包括1918年的“西班牙”流感，这是有史以来最致命的爆发之一，在全球范围内造成3000万至5000万人死亡，1957年的“亚洲”流感和1968年的“香港”流感。出于更好地了解流感演变的需要，我们开发了灵活的方案，使其能够将大规模测序技术应用于高度可变的流感基因组。在这里，我们报告了人类甲型流感病毒209个完整基因组的测序结果，共包含2，821，103个核苷酸。除了显著增加公开的完整流感病毒基因组的数量外，我们还在前209个基因组中发现了几个异常，这些异常表明了流感传播和进化的动态性质。这项新的大规模测序工作有望提供流感病毒演变及其通过人类和动物群体传播模式的更全面的图景。该项目的所有数据都将立即存入公共档案馆。
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(1,2). 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(3). 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.