Co-existence of major and minor viral populations from two different origins in patients secondarily infected with dengue virus serotype 2 in Bangkok
Co-existence of major and minor viral populations from two different origins in patients secondarily infected with dengue virus serotype 2 in Bangkok
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DOI：
10.1016/j.bbrc.2011.08.069
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发表时间：
2011-09-16
影响因子：
3.1
通讯作者：
Ikuta, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Puiprom, Orapim;Yamashita, Akifumi;Ikuta, Kazuyoshi
一般来说，RNA病毒表现出显着的遗传多样性，有时会影响感染宿主中的病毒适应性，也可能影响致病性。登革病毒（DENV）由四种抗原性不同的血清型组成。DENV的所有血清型均可引起轻度至重度登革热疾病。在这项研究中，我们检查了从2010年在曼谷二次感染血清2型（DENV-2）的四名患者中获得的血浆中DENV的序列变异。血浆来源的RNA在包括包膜（E）蛋白基因的大部分结构域III的区域直接进行逆转录酶（RT）-聚合酶链反应（PCR），并对获得的PCR产物进行克隆测序。使用从每个患者测序的19-20个克隆（总共78个）加上来自公共数据库的601个对应序列，系统发育分析显示核酸序列落入具有明显不同起源的两个簇。有趣的是，所有患者给出的序列表明他们携带的病毒群体含有2、3或5个遗传变异，这些变异由一个主要变异加上一个或多个次要变异组成。三名患者显示来自一个簇的主要变异加上来自另一个簇的一个或多个次要组分，而一名患者显示来自单个簇的主要和次要变异。因此，可以得出结论，属于两种不同遗传谱系的DENV于2010年在曼谷共同传播。对于这两个基因型簇，在推导的氨基酸位置346（即H346 Y）处的H或Y也存在明显差异，这与我们的序列和来自公共数据库的601序列一致。因此，引入人类个体的混合病毒基因型之一似乎被随机选择为携带病毒群体的主要组分，并且该过程的动态可能会影响病毒进化和疾病严重程度。(C)2011 Elsevier Inc. All rights reserved.
Generally, RNA viruses exhibit significant genetic diversity that sometimes effect viral fitness in infected hosts and probably also pathogenesis. Dengue viruses (DENVs) consist of four antigenically distinct sertypes. All the serotypes of DENV can cause mild to severe dengue illnesses. In this study, we examined the sequence variation of DENV in plasma obtained from four patients living in Bangkok who had been secondarily infected with serotype 2 (DENV-2) in 2010. The plasma-derived RNA was directly subjected to reverse transcriptase (RT)-polymerase chain reaction (PCR) at a region including most of domain III of the envelope (E) protein gene, and the PCR products obtained were subjected to clonal sequencing. Using 19-20 clones sequenced from each patient (78 total) plus 601 corresponding sequences from a public database, phylogenetic analysis revealed that the nucleic acid sequences fell into two clusters with clearly different origins. Interestingly, all patients gave sequences indicating that they carried viral populations containing 2,3 or 5 genetic variants that consisted of one major variant plus one or more minor variants. Three patients showed a major variant from one cluster plus one or more minor components from the other while one showed major and minor variants from a single cluster. Thus, it can be concluded that DENV belonging to two different genetic lineages were co-circulated in Bangkok in 2010. For these two genotype clusters there was also a clear difference in H or Y at the deduced amino acid position 346 (i.e. H346Y) that was consistent for our sequences and 601 sequences from the public database. Thus, one among the mixed viral genotypes introduced into human individuals seems to be variably selected as the predominant component of the carried viral population, and it is possible that the dynamics of this process could influence virus evolution and disease severity. (C) 2011 Elsevier Inc. All rights reserved.