Genetic evolution and tropism of transmissible gastroenteritis coronaviruses.
Genetic evolution and tropism of transmissible gastroenteritis coronaviruses.
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DOI：
10.1016/0042-6822(92)91195-z
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发表时间：
1992-09
期刊：
影响因子：
3.7
通讯作者：
Enjuanes L
中科院分区：
文献类型：
--
作者：
Sánchez CM;Gebauer F;Suñé C;Mendez A;Dopazo J;Enjuanes L
传染性胃肠炎病毒（TGEV）是1946年首次分离到的肠道致病性冠状病毒。非肠道致病性猪呼吸道冠状病毒（PRCV）来源于TGEV。根据它们的RNA序列，已经确定了TGEV抗原簇的六种欧洲PRCV和五种冠状病毒之间的遗传关系。六个PRCV的S蛋白具有从位置21开始的224个氨基酸的相同缺失。缺失区包括TGEV S糖蛋白的抗原位点C和B。有趣的是，两种具有呼吸嗜性的病毒（NEB 72和TOY 56）具有大小与肠道病毒相似的S蛋白。NEB 72和TOY 56病毒与肠道病毒在S蛋白中有2和15个特异性氨基酸差异。4个改变的残基（NEB 72分离株的aa 219和TOY 56的as 92、94和218）位于PRCV中存在的缺失内，可能涉及赋予TGEV肠向性的受体结合位点（RBS）。病毒用来感染ST细胞的第二个RBS可能位于S糖蛋白A和D位点之间的保守区域，因为对这些位点特异的单克隆抗体抑制病毒与ST细胞的结合。一个进化树有关13个肠道和呼吸道分离株已被提出。根据这棵树，一个主要的病毒谱系是从1941年左右流行的最近的祖先病毒进化而来的。由此，次级谱系依次起源于PUR46、NEB 72、TOY 56、MIL65、BR 170和PRCV。对TGEV相关冠状病毒起源的最小二乘估计显示，随着时间的推移，突变的固定具有显著的恒定性，即存在一个定义明确的分子钟。计算出TGEV相关病毒的突变固定率为每个位点每年7 ± 2 × 10−4个核苷酸替换。该比率福尔斯落在其他RNA病毒报告的范围内。在TGEV的进化过程中发生了点突变和重组事件。
Transmissible gastroenteritis virus (TGEV) is an enteropathogenic coronavirus isolated for the first time in 1946. Nonenteropathogenic porcine respiratory coronaviruses (PRCVs) have been derived from TGEV. The genetic relationship among six European PRCVs and five coronaviruses of the TGEV antigenic cluster has been determined based on their RNA sequences. The S protein of six PRCVs have an identical deletion of 224 amino acids starting at position 21. The deleted area includes the antigenic sites C and B of TGEV S glycoprotein. Interestingly, two viruses (NEB72 and TOY56) with respiratory tropism have S proteins with a size similar to the enteric viruses. NEB72 and TOY56 viruses have in the S protein 2 and 15 specific amino acid differences with the enteric viruses. Four of the residues changed (aa 219 of NEB72 isolate and as 92, 94, and 218 of TOY56) are located within the deletion present in the PRCVs and may be involved in the receptor binding site (RBS) conferring enteric tropism to TGEVs. A second RBS used by the virus to infect ST cells might be located in a conserved area between sites A and D of the S glycoprotein, since monoclonal antibodies specific for these sites inhibit the binding of the virus to ST cells. An evolutionary tree relating 13 enteric and respiratory isolates has been proposed. According to this tree, a main virus lineage evolved from a recent progenitor virus which was circulating around 1941. From this, secondary lineages originated PUR46, NEB72, TOY56, MIL65, BR170, and the PRCVs, in this order. Least squares estimation of the origin of TGEV-related coronaviruses showed a significant constancy in the fixation of mutations with time, that is, the existence of a well-defined molecular clock. A mutation fixation rate of 7 ± 2 × 10−4 nucleotide substitutions per site and per year was calculated for TGEV-related viruses. This rate falls in the range reported for other RNA viruses. Point mutations and probably recombination events have occurred during TGEV evolution.
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