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首页> 外文期刊>Virus Genes >Evidence for inter- and intra-genotypic variations in dengue serotype 4 viruses representing predominant and non-predominant genotypes co-circulating in Thailand from 1977 to 2001.
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Evidence for inter- and intra-genotypic variations in dengue serotype 4 viruses representing predominant and non-predominant genotypes co-circulating in Thailand from 1977 to 2001.

机译：1977年至2001年在泰国流行的代表主要和非主要基因型的登革热4型病毒基因型间和基因内变异的证据。

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摘要

In order to characterize viral genetic variation among predominant and non-predominant genotypes of Thai dengue serotype 4 viruses (DENV-4) and follow mutations that occur during virus evolution, we performed a comparative analysis of the complete genomic sequences of six DENV-4 isolates representing three genotypes (I, IIA, and III) co-circulating in Thailand over a 24-year period. The results revealed [1] remarkable genetic variation in the viral genome between predominant and non-predominant genotypes; [2] inter-genotype-specific amino acid and nucleotide mutations in most regions of the viral genome; [3] more amino acid and nucleotide substitutions in later as compared to earlier isolates for predominant genotype I strains; [4] a single nucleotide substitution at nucleotide position 77 of the 5-'NTR of two non-predominant genotype III strains that disrupted a small conserved 3'stem-loop (SL) in the cyclization sequence required for virus replication; [5] a high degree of conservation of PrM/M and NS2B proteins, and the 5'-NTR in predominant genotype I strains with no mutations observed over the 24-year period of observation; and [6] no molecular markers that appeared to correlate with disease severity. Several mutations identified in this study might have a significant impact on the persistence of virus in the population, including one in the 5'-NTR that disrupted a small, highly conserved 3'SL2 structure at the terminus of the cyclized 5'-3' RNA sequences in two genotype III strains, and three amino acid (aa) charge change mutations in the E and NS5 proteins of genotype I strains. The conserved 3'-SL structure may be a target for antiviral drug development.
机译：为了表征泰国登革热血清型4型病毒（DENV-4）的主要和非主要基因型之间的病毒遗传变异，并跟踪在病毒进化过程中发生的突变，我们对六个DENV-4分离株的完整基因组序列进行了比较分析代表在24年内在泰国共同流行的三种基因型（I，IIA和III）。结果显示[1]优势基因型和非优势基因型之间病毒基因组的显着遗传变异; [2]病毒基因组大多数区域中基因型间特定的氨基酸和核苷酸突变; [3]与早期分离的主要基因型I菌株相比，晚期的氨基酸和核苷酸取代更多; [4]在两个非主要基因型III株的5-'NTR核苷酸位置77处的单个核苷酸取代，破坏了病毒复制所需的环化序列中小的保守3'茎-环（SL）; [5]高度保守的PrM / M和NS2B蛋白，以及在24年观察期内未观察到突变的主要基因型I株中的5'-NTR; [6]没有分子标记与疾病的严重程度相关。在这项研究中鉴定出的几种突变可能会对病毒在人群中的持久性产生重大影响，包括5'-NTR中的一种突变破坏了环化5'-3'末端小的，高度保守的3'SL2结构。两个基因型III菌株的RNA序列，以及基因型I菌株E和NS5蛋白的三个氨基酸（aa）电荷变化突变。保守的3'-SL结构可能是抗病毒药物开发的目标。

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