The molecular epidemiology of dengue virus serotype 4 in Bangkok, Thailand
The molecular epidemiology of dengue virus serotype 4 in Bangkok, Thailand
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DOI：
10.1016/j.virol.2004.08.003
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发表时间：
2004-11-10
期刊：
影响因子：
3.7
通讯作者：
Holmes, EC
中科院分区：
文献类型：
--
作者：
Klungthong, C;Zhang, CL;Holmes, EC
登革热是泰国的一个主要公共卫生问题，所有四种病毒血清型共同传播。登革病毒血清型4（DENV-4）是最不常采样的血清型，尽管它经常与继发感染期间的出血热有关。为了确定形成DENV-4遗传多样性的进化力量，特别是其不断变化的流行率是否可以归因于病毒基因组中的适应性进化的实例，我们在泰国曼谷进行了大规模的DENV-4分子流行病学分析，使用E基因和完整的编码区序列。该分析揭示了在单一时间内单一地点内广泛的遗传多样性，包括发现DENV-4的新的和不同的基因型，以及连续谱系更替的模式。我们还记录了该血清型的最高平均进化变化率，每个位点每年有1.072 × 10（-3）个核苷酸替换。然而，尽管存在这种丰富的遗传变异，但在DENV-4的任何基因、密码子或谱系中没有适应性进化的证据，在NS 2A中观察到的非同义替换率最高。因此，DENV-4谱系随时间的快速更替最有可能是病毒基因组中高速率的有害突变与载体群体大小的季节性波动相结合的结果。(C)2004年爱思唯尔公司All rights reserved.
Dengue represents a major public health problem in Thailand, with all four viral serotypes co-circulating. Dengue virus serotype 4 (DENV-4) is the least frequently sampled serotype, although one that is often associated with hemorrhagic fever during secondary infection. To determine the evolutionary forces shaping the genetic diversity of DENV-4, and particularly whether its changing prevalence could be attributed to instances of adaptive evolution in the viral genome, we undertook a large-scale molecular epidemiological analysis of DENV-4 in Bangkok, Thailand, using both E gene and complete coding region sequences. This analysis revealed extensive genetic diversity within a single locality at a single time, including the discovery of a new and divergent genotype of DENV-4, as well as a pattern of continual lineage turnover. We also recorded the highest average rate of evolutionary change for this serotype, at 1.072 x 10(-3) nucleotide substitutions per site, per year. However, despite this abundant genetic variation, there was no evidence for adaptive evolution in any gene, codon, or lineage of DENV-4, with the highest rate of nonsynonymous substitution observed in NS2A. Consequently, the rapid turnover of DENV-4 lineages through time is most likely the consequence of a high rate of deleterious mutation in the viral genome coupled to seasonal fluctuations in the size of the vector population. (C) 2004 Elsevier Inc. All rights reserved.