Hypothesis: Both appearance and disappearance of viruses are controlled by the accumulation of amino acid substitution in receptor binding domain

已知RNA病毒基因组的进化速度比普通DNA基因组快10^6倍。这种较高的进化速度被认为与病毒在人类世界的出现和消失有关。为了了解细胞受体分子与病毒粒子受体结合域之间的相互作用，分析了病毒编码蛋白中的核苷酸和氨基酸替换。根据EV70衣壳蛋白VP1的核苷酸序列，构建了一个精细的系统发育树。通过分析分离株间的系统发育关系和取代模式，推导出原始核苷酸序列。其进化速率估计为5 × 10^<-3>/位点/年，而另一种引起急性出血性结膜炎的病原体柯萨奇病毒A24变体的3C蛋白酶区域的进化速率计算为4.9 × 10^<-3>/位点/年。利用一种能够阻断EV70感染的单克隆抗体，用从Hela细胞mRNA中提取的cDNA文库转染COS细胞进行筛选。受体分子位于易感细胞的表面，其核苷酸序列与调节免疫重要分子功能的分子的核苷酸序列相同。

The genome of the RNA viruses is known to evolve 10^6 times faster than ordinary DNA genome. This higher evolutionary rate is thought to be linked with both appearance and disappearance of the viruses in human world. To understand the interaction between cellular receptor molecule and receptor binding domain of the virion the nucleotide and amino acid substitutions in virus encoded proteins were analyzed. According to the nucleotide sequences of EV70 capsid protein VP1 we have constructed a fine phylogenetic tree. By analyzing the phylogenetic relationship and the substitution pattern among the isolates we deduced the original nucleotide sequence. The evolutionary rate was estimated to be 5x10^<-3>/site/year, whereas the rate of the 3C protease region of coxsackievirus A24 variant, an another agent that cause acute hemorrhagic conjunctivitis, was calculated to be 4.9x10^<-3>/site/year. Using a monoclonalantibody that is capable of blocking EV70 infection screening of the COS cells transfected with cDNA library derived from Hela cell mRNA was carried out by socalled "panning" method. The receptor molecules are found to be located on the surface of the susceptive cells and has the nucleotide sequence identical to that of the molecule which regulates a function of an immunologically important molecule.