Genomic events contributing to the high prevalence of amantadine-resistant influenza A/H3N2
Genomic events contributing to the high prevalence of amantadine-resistant influenza A/H3N2
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导致金刚烷胺抗药性甲型/H3N2流感高流行的基因组事件
DOI：
10.3851/imp1538
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发表时间：
2010
影响因子：
1.2
通讯作者：
Hiroshi Suzuki
中科院分区：
文献类型：
--
作者：
H. Zaraket;R. Saito;Yasushi Suzuki;Yoshiyuki Suzuki;Isolde Caperig;Clyde Dapat;I. Shabana;T. Baranovich;Hiroshi Suzuki
背景自2005年以来，具有金刚烷胺耐药性的甲型流感/H3 N2病毒（属于N谱系）的流行率在全球范围内显著增加，该病毒在M2蛋白中具有S31 N突变，在其HA 1亚基中具有S193 F和D225 N取代。本研究的目的是阐明基因组事件有助于进化和连续性的N-系金刚烷胺耐药病毒。方法测定2006 - 2008年日本分离的A/H3 N2亚型（包括金刚烷胺耐药和敏感型）的全基因组序列，并与数据库中获得的分离株进行遗传学比较。结果根据全基因组序列分析，N系可进一步分为3个遗传相关的分支：N1（2005-2007年A/威斯康星州/67/2005类金刚烷胺耐药病毒）、N2（2007年金刚烷胺敏感病毒）和N3（2007 - 2008年A/布里斯班/10/2007类金刚烷胺耐药病毒）。2006/2007年季节显示，除了N2敏感病毒外，分支N1和N3的金刚烷胺抗性病毒的抗原变体也存在共循环。在2007/2008赛季，分支N3金刚烷胺抗性谱系占主导地位，并取代其他菌株。每个单独的片段的系统发育分析表明，N2和N3产生从两个独立的重配事件涉及进化枝N1病毒和前N-谱系株。结论我们的数据表明，几个重配事件的金刚烷胺耐药的A/H3 N2菌株的进化，因此，该谱系的成功传播。虽然金刚烷胺耐药是由M2蛋白中的单个氨基酸突变引起的，但涉及多个基因的全基因组调整似乎是获得耐药病毒的有效复制和传播所必需的。这种调整可以通过不同病毒谱系之间的片段重组来实现。
Background The prevalence of amantadine-resistant influenza A/H3N2 viruses (belonging to the N-lineage), possessing an S31N mutation in the M2 protein and S193F and D225N substitutions in their HA1 subunit, has significantly increased worldwide since 2005. The aim of this study was to clarify the genomic events contributing to the evolution and continuity of the N-lineage amantadine-resistant viruses. Methods The full genome sequence of A/H3N2 isolates, including both amantadine-resistant and amantadine-sensitive viruses, collected in Japan between 2006 and 2008, was determined and phylogenetically compared with isolates obtained from the database. Results On the basis of the full genome sequence analysis, the N-lineage could be further divided into three genetically related clades: N1 (A/Wisconsin/67/2005-like amantadine-resistant viruses from years 2005–2007), N2 (amantadine-sensitive viruses from 2007) and N3 (A/Brisbane/10/2007-like amantadine-resistant viruses from 2007 and 2008). The 2006/2007 season showed cocirculation of antigenic variants of amantadine-resistant viruses of clades N1 and N3 in addition to the N2-sensitive viruses. In the 2007/2008 season, the clade N3 amantadine-resistant lineage dominated and replaced other strains. Phylogenetic analysis of each individual segment suggested that N2 and N3 were generated from two independent reassortment events involving clade N1 viruses and pre-N- lineage strains. Conclusions Our data show that several reassortment events have contributed to the evolution of amantadine-resistant A/H3N2 strains and, consequently, to the successful spread of this lineage. Although amantadine resistance is caused by single amino acid mutations in the M2 protein, genome-wide adjustment involving multiple genes appears to be necessary to obtain efficient replication and transmission of resistant viruses. Such adjustments are attainable through reassortment of segments among different virus lineages.