Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia.
Virology. 2010 Mar 15;398(2):262-72. doi: 10.1016/j.virol.2009.12.012. Epub 2010 Jan 12.
Previously different authors described various flavivirus mutants with high affinity to cell glycosaminoglycans and low neuroinvasiveness in mice that were obtained consequently passages in cell cultures or in ticks. In present study the analysis of TBEV isolates has shown existence of GAG-binding variants in natural virus population. Affinity to GAG has been evaluated by sorption on heparin-Sepharose. GAG-binding phenotype corresponds to such virus properties, like small plaque phenotype in PEK cells, absence of hemagglutination at pH 6.4, and low neuroinvasiveness in mice. Mutations increasing charge of E protein were necessary but not sufficient for acquisition of GAG-binding phenotype. Molecular modeling and molecular dynamics simulation have shown that the flexibility of E protein molecule could bear influence on the phenotypic manifestation of substitutions increasing charge of the virions.
先前不同的作者描述了各种具有高亲和力与细胞糖胺聚糖和低神经侵袭性的黄病毒突变体，这些突变体是在细胞培养物或蜱中连续传代获得的。在本研究中，对 TBEV 分离株的分析表明，天然病毒群体中存在 GAG 结合变体。通过肝素-琼脂糖的吸附来评估对 GAG 的亲和力。GAG 结合表型与病毒的某些特性相对应，如在 PEK 细胞中形成小噬菌斑、在 pH 值为 6.4 时不发生血凝、以及在小鼠中神经侵袭性低。增加 E 蛋白电荷的突变是获得 GAG 结合表型所必需的，但不是充分的。分子建模和分子动力学模拟表明，E 蛋白分子的灵活性可能对增加病毒电荷的取代的表型表现产生影响。
