Inter- and intra-host viral diversity in a large seasonal DENV2 outbreak.
Inter- and intra-host viral diversity in a large seasonal DENV2 outbreak.
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DOI：
10.1371/journal.pone.0070318
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kallas EG
中科院分区：
文献类型：
--
作者：
Romano CM;Lauck M;Salvador FS;Lima CR;Villas-Boas LS;Araújo ES;Levi JE;Pannuti CS;O'Connor D;Kallas EG
宿主间和宿主内水平的高遗传多样性是RNA病毒的标志，这是由于其基因组复制的易错性。几个研究小组已经使用不同的RNA病毒深度测序方法评估了病毒变异的程度。尽管大部分工作都致力于研究导致人类慢性感染的病原体，但很少有研究调查节肢动物传播的急性病毒感染。我们使用两种不同的方法对来自巴西大爆发中典型和严重病例样本的10个DENV 2分离株的全基因组进行了深度测序。对共有基因组的分析证实，与两年前在另一个城市由相同病毒引起的先前流行相比，2010年流行的程度更大（遗传距离分别为0.002和0.0008）。 对宿主内病毒种群的分析显示了高水平的保守性。在排除454/Roche产生的序列的同聚物区域后，我们发现每个基因组群体有10至44个可变位点，频率> 1%，导致宿主内遗传多样性非常低。虽然在宿主内水平上高达60%的所有可变位点是非同义变化，但只有10%的宿主间变异性是由非同义突变引起的，这表明在群体水平上进行了纯化选择。尽管RNA依赖性RNA聚合酶具有易错性，但登革病毒保持低水平的宿主内变异性。
High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
11.8
作者：
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DOI：
10.1073/pnas.0712130105
发表时间：
2008-05-13
影响因子：
11.1
作者：
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通讯作者：
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