Integrin-using rotaviruses bind α2β1 integrin α2 I domain via VP4 DGE sequence and recognize αXβ2 and αVβ3 by using VP7 during cell entry
Integrin-using rotaviruses bind α2β1 integrin α2 I domain via VP4 DGE sequence and recognize αXβ2 and αVβ3 by using VP7 during cell entry
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DOI：
10.1128/jvi.77.18.9969-9978.2003
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Coulson, BS
中科院分区：
文献类型：
--
作者：
Graham, KL;Halasz, P;Coulson, BS
整合素alpha2beta1、alphaXbeta2和alphaVbeta3与轮状病毒的细胞附着和进入有关。病毒刺突蛋白VP4在308 ~ 310个氨基酸位置含有alpha2beta1配体序列DGE，外衣壳蛋白VP7含有alphaXbeta2配体序列GPR。为了确定所涉及的病毒蛋白和序列，并确定alpha2beta1、alphaXbeta2和alphaVbeta3的作用，我们分析了轮状病毒及其重组体利用这些整合素进行细胞结合和感染的能力，以及肽DGEA和GPRP对这些事件的影响。许多实验室适应的人、猴和牛病毒使用整合素，而所有猪病毒都不依赖整合素。使用整合素的轮状病毒株都与所有三种整合素相互作用。整合素使用与VP4血清型相关，独立于唾液酸使用。轮状病毒重组分析以及整合素转染细胞的病毒结合和感染性检测表明，VP4与alpha2beta1结合，VP7在结合后阶段与alphaXbeta2和alphaVbeta3相互作用。gea抑制轮状病毒与alpha2beta1的结合和传染性，而GPRP与alphaXbeta2的结合抑制传染性，但不结合。VP4截断的VP5*亚基，表达为谷胱甘肽s转移酶融合蛋白，结合表达的alpha2 I结构域。D308和G309在VP5*中的丙氨酸诱变消除了VP5*与α 2 I结构域的结合。在一个新的过程中，使用整合素的病毒通过VP4中的DGE结合alpha2beta1的alpha2 I结构域，并通过VP7与alphaXbeta2（通过GPR）和alphaVbeta3相互作用，促进细胞进入和感染。
Integrins alpha2beta1, alphaXbeta2, and alphaVbeta3 have been implicated in rotavirus cell attachment and entry. The virus spike protein VP4 contains the alpha2beta1 ligand sequence DGE at amino acid positions 308 to 310, and the outer capsid protein VP7 contains the alphaXbeta2 ligand sequence GPR. To determine the viral proteins and sequences involved and to define the roles of alpha2beta1, alphaXbeta2, and alphaVbeta3, we analyzed the ability of rotaviruses and their reassortants to use these integrins for cell binding and infection and the effect of peptides DGEA and GPRP on these events. Many laboratory-adapted human, monkey, and bovine viruses used integrins, whereas all porcine viruses were integrin independent. The integrin-using rotavirus strains each interacted with all three integrins. Integrin usage related to VP4 serotype independently of sialic acid usage. Analysis of rotavirus reassortants and assays of virus binding and infectivity in integrin-transfected cells showed that VP4 bound alpha2beta1, and VP7 interacted with alphaXbeta2 and alphaVbeta3 at a postbinding stage. DGEA inhibited rotavirus binding to alpha2beta1 and infectivity, whereas GPRP binding to alphaXbeta2 inhibited infectivity but not binding. The truncated VP5* subunit of VP4, expressed as a glutathione S-transferase fusion protein, bound the expressed alpha2 I domain. Alanine mutagenesis of D308 and G309 in VP5* eliminated VP5* binding to the alpha2 I domain. In a novel process, integrin-using viruses bind the alpha2 I domain of alpha2beta1 via DGE in VP4 and interact with alphaXbeta2 (via GPR) and alphaVbeta3 by using VP7 to facilitate cell entry and infection.