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可传播性胃肠炎冠状病毒PUR46簇嗜性的分子基础

Molecular bases of tropism in the PUR46 cluster of transmissible gastroenteritis coronaviruses.

作者信息

Ballesteros M L, Sánchez C M, Martin-Caballero J, Enjuanes L

机构信息

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain.

出版信息

Adv Exp Med Biol. 1995;380:557-62. doi: 10.1007/978-1-4615-1899-0_89.

DOI:10.1007/978-1-4615-1899-0_89
PMID:8830541
Abstract

Transmissible gastroenteritis coronavirus (TGEV) infects both, the enteric and the respiratory tract of swine. S protein, that is recognized by the cellular receptor, has been proposed that plays an essential role in controlling the dominant tropism. The genetic relationship of S gene from different enteric strains and non-enteropathogenic porcine respiratory coronaviruses (PRCVs) was determined. A correlation between tropism and the genetic structure of the S gene was established. PRCVs, derived from enteric isolates have a large deletion at the N-terminus of the S protein. Interestingly, two respiratory isolates, attenuated Purdue type virus (PTV-ATT) and Toyama (TOY56) have a full-length S gene. PTV-ATT has two specific amino acid differences with the S protein of the enteric viruses. One is located around position 219, within the deleted area, suggesting that alterations around this amino acid may result in the loss of enteric tropism. To study the role of different genes in tropism, a cluster of viruses closely related to PUR46 strain was analyzed. All of them have been originated by accumulating point mutations from a common, virulent isolate which infected the enteric tract. During their evolution these viruses have lost, virulence first, and then, enteric tropism. Sequencing analysis proved that enteric tropism could be lost without changes in ORFs 3a, 3b, 4, 6, and 7, and in 3'-end untranslated regions (3'-UTR). To study the role of the S protein in tropism recombinants were obtained between an enteric and a respiratory virus of this cluster. Analysis of the recombinants supported the hypothesis on the role in tropism of S protein domain around position 219.

摘要

传染性胃肠炎冠状病毒(TGEV)可感染猪的肠道和呼吸道。细胞受体可识别的S蛋白被认为在控制主要嗜性方面起着至关重要的作用。确定了来自不同肠道毒株和非肠道致病性猪呼吸道冠状病毒(PRCV)的S基因的遗传关系。建立了嗜性与S基因遗传结构之间的相关性。源自肠道分离株的PRCV在S蛋白的N端有一个大的缺失。有趣的是,两种呼吸道分离株,减毒的普渡型病毒(PTV-ATT)和富山株(TOY56)具有全长S基因。PTV-ATT与肠道病毒的S蛋白有两个特定的氨基酸差异。一个位于大约219位,在缺失区域内,这表明该氨基酸周围的改变可能导致肠道嗜性丧失。为了研究不同基因在嗜性中的作用,分析了一组与PUR46毒株密切相关的病毒。它们都是由一个感染肠道的常见强毒株积累点突变而产生的。在它们的进化过程中,这些病毒首先失去了毒力,然后失去了肠道嗜性。测序分析证明,在开放阅读框3a、3b、4、6和7以及3'端非翻译区(3'-UTR)没有变化的情况下,肠道嗜性可能会丧失。为了研究S蛋白在嗜性中的作用,在该组的一种肠道病毒和一种呼吸道病毒之间获得了重组体。重组体的分析支持了关于219位左右S蛋白结构域在嗜性中作用的假设。

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