ANALYSIS OF FLAVIVIRUS ENVELOPE PROTEINS REVEALS VARIABLE DOMAINS THAT REFLECT THEIR ANTIGENICITY AND MAY DETERMINE THEIR PATHOGENESIS
ANALYSIS OF FLAVIVIRUS ENVELOPE PROTEINS REVEALS VARIABLE DOMAINS THAT REFLECT THEIR ANTIGENICITY AND MAY DETERMINE THEIR PATHOGENESIS
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DOI：
10.1016/0168-1702(94)00090-y
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发表时间：
1995-03-01
期刊：
影响因子：
5
通讯作者：
GOULD, EA
中科院分区：
文献类型：
--
作者：
GRITSUN, TS;HOLMES, EC;GOULD, EA
对黄病毒中和、减毒和趋向性的分子基础的研究表明，包膜基因不同部分的氨基酸取代可能是导致表型改变的原因。然而，将特定替代与个体特征联系起来已被证明是困难的。通过序列比对和滑动窗口对所有已知的蜱传黄病毒包膜蛋白进行比较分析，揭示了分布在整个包膜蛋白编码区的氨基酸变异簇。与蚊媒黄病毒的进一步比较揭示了整个包膜蛋白序列的变异性基本相同，尽管这些病毒的假定 B 结构域内存在重大差异，这可能反映了它们不同的进化发展。大多数表型变异特性，例如血清型差异、疫苗株的变异特征、向性改变和中和逃逸突变体，都映射在变量簇内。因此，我们提出自然诱变和选择可能发生在不破坏二级和三级E蛋白结构的特定位点，并且可变簇代表定义抗原性、嗜性和发病机制的包膜蛋白的暴露表面氨基酸。
Studies on the molecular basis of flavivirus neutralisation, attenuation and tropism indicate that amino acid substitutions, in different parts of the envelope gene, may be responsible for the altered phenotypes. However, the association of particular substitutions with individual characteristics has proven difficult. Comparative analysis of all known tick-borne flavivirus envelope proteins through sequence alignment and a sliding window, reveals clusters of amino acid variation distributed throughout the envelope protein coding region. Further comparison with mosquito-borne flaviviruses reveals essentially the same profile of variability throughout the envelope protein sequence although there is a major difference within the postulated B domain of these viruses which may reflect their different evolutionary development. Most phenotypically variant properties, such as serotypic differences, variants characteristic of vaccine strains, altered tropisms and neutralisation escape mutants, map within the variable clusters. Thus, we propose that natural mutagenesis and selection may occur at specific sites that do not destroy the secondary and tertiary E protein structure and that the variable clusters represent the exposed surface amino acids of the envelope protein defining antigenicity, tropicity and pathogenesis.