Whole genome characterization, phylogenetic and genome signature analysis of human pandemic H1N1 virus in Thailand, 2009-2012.

Whole genome characterization, phylogenetic and genome signature analysis of human pandemic H1N1 virus in Thailand, 2009-2012.
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DOI:
10.1371/journal.pone.0051275
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Poovorawan Y
Poovorawan Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Makkoch J;Suwannakarn K;Payungporn S;Prachayangprecha S;Cheiocharnsin T;Linsuwanon P;Theamboonlers A;Poovorawan Y

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2009-2012年,泰国发生了三波人流感大流行。需要对pH 1 N1的基因组特征和进化进行表征,以阐明造成多波大流行的方面。40个全基因组序列和584个部分序列的pH 1 N1循环在泰国,分为第一,第二和第三波和大流行后的特征和77个基因组签名进行了分析。构建了HA基因和全基因组序列的系统发育树,计算了每个基因的替换率和dN/dS。系统发育分析表明,泰国的pH 1 N1循环模式不同,2009年5月的前两个分离株属于进化枝5,而进化枝5、6和7在泰国第一波pH 1 N1大流行期间共同循环。在第二波期间,进化枝8占主导地位,在第三波期间和大流行后期间,不同比例的pH 1 N1病毒属于进化枝8、11.1和11.2。pH 1 N1的突变分析揭示了许多适应性突变,这些适应性突变已经成为每个进化枝的特征,并且可能是泰国多个大流行波的原因,特别是关于进化枝11.1和11.2,如由PB 1基因的V731 I、G154 D、PA I330 V、HA A214 T、S160 G和S202 T证明的。泰国的pH 1 N1基因替换率为2.53×10−3±0.02(M2基因)至5.27×10−3±0.03(NA基因)/位点/年。以上结果表明,尽管dN/dS在所有8个基因中均处于纯化选择状态,但该病毒仍具有一定的适应性,可能是为了逃避宿主的免疫应答而在人体内滞留。由于泰国的pH 1 N1逐渐演变,持续监测对于评估和监测至关重要,以便为未来的流感活动做好准备并能够控制这些活动。
Three waves of human pandemic influenza occurred in Thailand in 2009–2012. The genome signature features and evolution of pH1N1 need to be characterized to elucidate the aspects responsible for the multiple waves of pandemic. Forty whole genome sequences and 584 partial sequences of pH1N1 circulating in Thailand, divided into 1st, 2nd and 3rd wave and post-pandemic were characterized and 77 genome signatures were analyzed. Phylogenetic trees of concatenated whole genome and HA gene sequences were constructed calculating substitution rate and dN/dS of each gene. Phylogenetic analysis showed a distinct pattern of pH1N1 circulation in Thailand, with the first two isolates from May, 2009 belonging to clade 5 while clades 5, 6 and 7 co-circulated during the first wave of pH1N1 pandemic in Thailand. Clade 8 predominated during the second wave and different proportions of the pH1N1 viruses circulating during the third wave and post pandemic period belonged to clades 8, 11.1 and 11.2. The mutation analysis of pH1N1 revealed many adaptive mutations which have become the signature of each clade and may be responsible for the multiple pandemic waves in Thailand, especially with regard to clades 11.1 and 11.2 as evidenced with V731I, G154D of PB1 gene, PA I330V, HA A214T S160G and S202T. The substitution rate of pH1N1 in Thailand ranged from 2.53×10−3±0.02 (M2 genes) to 5.27×10−3±0.03 per site per year (NA gene). All results suggested that this virus is still adaptive, maybe to evade the host's immune response and tends to remain in the human host although the dN/dS were under purifying selection in all 8 genes. Due to the gradual evolution of pH1N1 in Thailand, continuous monitoring is essential for evaluation and surveillance to be prepared for and able to control future influenza activities.
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