Rotaviruses interact with α4β7 and α4β1 integrins by binding the same integrin domains as natural ligands
Rotaviruses interact with α4β7 and α4β1 integrins by binding the same integrin domains as natural ligands
复制标题
DOI：
10.1099/vir.0.81102-0
复制
发表时间：
2005-12-01
影响因子：
3.8
通讯作者：
Coulson, BS
中科院分区：
文献类型：
--
作者：
Graham, KL;Fleming, FE;Coulson, BS
A组轮状病毒是主要的肠道病原体，其外衣壳蛋白VP7表达潜在的α 4B1和α 4 β 7整合素配体序列Leu-Asp-Val和Leu-Asp-IIe，其刺突蛋白VP4表达IIe-Asp-Ala。猴轮状病毒SA11可以利用重组α 4 β 1作为细胞受体。本研究在VP4中发现了新的潜在的α 4 β 1、α 4 β 7和α 9 β 1整合素配体序列Tyr-Gly-Leu。研究表明，几种人类和猴子轮状病毒；结合4 1和4 7，但不是9 1。与α 4 β 1结合介导猴轮状病毒的传染性和生长，与α 4 β 7结合介导其传染性。猪轮状病毒与α 4整合素在结合后阶段相互作用以促进感染。α 4 β 1的激活增加了轮状病毒的传染性。用含有C/A整合素配体序列tir - gly - leu和IIe-Asp-Ala的肽处理细胞可消除病毒与α 4整合素的结合和传染性。相比之下，轮状病毒对α 4整合素的识别不受含有Leu-Asp-Val序列的肽或VP7 Leu-Asp-Val序列突变的影响。通过轮状病毒重组证明VP4参与轮状病毒对α 4 β 1的识别。α 4表面环的交换和点诱变表明，轮状病毒需要与天然α 4整合素配体相同的α 4残基和结构域进行结合：粘膜定位蛋白细胞粘附分子-1、纤维连接蛋白和血管细胞粘附分子-1。一些轮状病毒能够通过识别与天然α 4配体相同的α 4亚基结构域，利用α 4 β 7和α 4 β 1结合或进入细胞。
Group A rotaviruses are major intestinal pathogens that express potential alpha 4B1 and alpha 4 beta 7 integrin ligand sequences Leu-Asp-Val and Leu-Asp-IIe in their outer capsid protein VP7, and IIe-Asp-Ala in their spike protein VP4. Monkey rotavirus SA11 can use recombinant alpha 4 beta 1 as a cellular receptor. In this study a new potential alpha 4 beta 1, alpha 4 beta 7 and alpha 9 beta 1 integrin ligand sequence, Tyr-Gly-Leu, was identified in VP4. It was shown that several human and monkey rotaviruses ;bound alpha 4 beta 1 and alpha 4 beta 7, but not alpha 9 beta 1. Binding to alpha 4 beta 1 mediated the infectivity and growth of monkey rotaviruses, and binding to alpha 4 beta 7 mediated their infectivity. A porcine rotavirus interacted with alpha 4 integrins at a post-binding stage to facilitate infection. Activation of alpha 4 beta 1 increased rotavirus infectivity. Cellular treatment with peptides containing the C/A integrin ligand sequences Tyr-Gly-Leu and IIe-Asp-Ala eliminated virus binding to alpha 4 integrins and infectivity. In contrast, rotavirus recognition of alpha 4 integrins was unaffected by a peptide containing the sequence Leu-Asp-Val or by a mutation in the VP7 Leu-Asp-Val sequence. VP4 involvement in rotavirus recognition of alpha 4 beta 1 was demonstrated with rotavirus reassortants. Swapping and point mutagenesis of alpha 4 surface loops showed that rotaviruses required the same alpha 4 residues and domains for binding as the natural alpha 4 integrin ligands: mucosal addressin cell adhesion molecule-1, fibronectin and vascular cell adhesion molecule-1. Several rotaviruses are able to use alpha 4 beta 7 and alpha 4 beta 1 for cell binding or entry, through the recognition of the same alpha 4-subunit domains as natural alpha 4 ligands.