Molecular evolution and the global reemergence of enterovirus D68 by genome-wide analysis
Molecular evolution and the global reemergence of enterovirus D68 by genome-wide analysis
复制标题
DOI：
10.1097/md.0000000000004416
复制
发表时间：
2016-08-01
期刊：
影响因子：
1.6
通讯作者：
Tsao, Kuo-Chien
中科院分区：
文献类型：
--
作者：
Gong, Yu-Nong;Yang, Shu-Li;Tsao, Kuo-Chien
人类肠道病毒D68（EV-D68）于1962年在美国首次报道；此后，1970年至2005年报告了一些病例，但在菲律宾（2008年）和美国（2014年）发生了2次疫情。然而，由于缺乏全基因组序列和分析，人们对这种全球重新出现的病毒的分子进化知之甚少。在这里，收集了所有公开可用的序列，包括来自 GenBank 的 147 个完整基因组和 1248 个部分基因组，并在进化枝和亚进化枝水平上进行了比较； 2014年在台湾分离的11个全基因组也被添加到数据库中。构建系统发育树来识别新的分支 B3，并代表菌株之间的分支循环。根据亚进化枝 B3 与 B1 和 B2 的比较，VP1 基因的核苷酸序列同一性为 94% 至 95%，当比较 A、C 和 D 时，VP1 基因的核苷酸序列同一性为 87% 至 91%。需要澄清进化枝循环模式，以改善对 EV-D68 的全球监测，尽管与常见肠道病毒 EV-71 相比，该病毒在进化枝之间的多样性较低。值得注意的是，2014年从台湾和中国分离出的重症病例是在B3亚支中发现的。台湾的一例重症病例是一名患有潜在血管免疫母细胞性T细胞淋巴瘤的女性患者，从该患者身上获取了支气管肺泡灌洗标本。尽管宿主因素在疾病严重程度中起着关键作用，但我们不能排除 EV-D68 可能引发临床症状或死亡的可能性。为了进一步研究 EV-D68 的遗传多样性，我们报告了通过比较亚进化枝 B3 与 B1 和 B2 鉴定的 34 个氨基酸 (aa) 多态性。 D 分支菌株的 VP1 基因中有 1 个氨基酸缺失和 2 个氨基酸插入，我们的 1 个 TW/2014 菌株在 50 个非翻译区中的缺失比之前报道的缺失更短。总之，发现了一个新的亚支、遗传插入缺失和全球菌株的多态性，阐明了 EV-D68 的进化和流行病学趋势，并将 11 个基因组添加到数据库中。病毒变异可能会导致疾病的严重程度和临床表现，需要进一步研究来调查遗传多样性与临床结果之间的关联。
Human enterovirus D68 (EV-D68) was first reported in the United States in 1962; thereafter, a few cases were reported from 1970 to 2005, but 2 outbreaks occurred in the Philippines (2008) and the United States (2014). However, little is known regarding the molecular evolution of this globally reemerging virus due to a lack of whole-genome sequences and analyses. Here, all publically available sequences including 147 full and 1248 partial genomes from GenBank were collected and compared at the clade and subclade level; 11 whole genomes isolated in Taiwan (TW) in 2014 were also added to the database. Phylogenetic trees were constructed to identify a new subclade, B3, and represent clade circulations among strains. Nucleotide sequence identities of the VP1 gene were 94% to 95% based on a comparison of subclade B3 to B1 and B2 and 87% to 91% when comparing A, C, and D. The patterns of clade circulation need to be clarified to improve global monitoring of EV-D68, even though this virus showed lower diversity among clades compared with the common enterovirus EV-71. Notably, severe cases isolated from Taiwan and China in 2014 were found in subclade B3. One severe case from Taiwan occurred in a female patient with underlying angioimmunoblastic T-cell lymphoma, from whom a bronchoalveolar lavage specimen was obtained. Although host factors play a key role in disease severity, we cannot exclude the possibility that EV-D68 may trigger clinical symptoms or death. To further investigate the genetic diversity of EV-D68, we reported 34 amino acid (aa) polymorphisms identified by comparing subclade B3 to B1 and B2. Clade D strains had a 1-aa deletion and a 2-aa insertion in the VP1 gene, and 1 of our TW/2014 strains had a shorter deletion in the 50 untranslated region than a previously reported deletion. In summary, a new subclade, genetic indels, and polymorphisms in global strains were discovered elucidating evolutionary and epidemiological trends of EV-D68, and 11 genomes were added to the database. Virus variants may contribute to disease severity and clinical manifestations, and further studies are needed to investigate the associations between genetic diversity and clinical outcomes.