Mason P W, Rieder E, Baxt B
Plum Island Animal Disease Center, U.S. Department of Agriculture, Greenport, NY 11944.
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1932-6. doi: 10.1073/pnas.91.5.1932.
Foot-and-mouth disease virus appears to initiate infection by binding to cells at an Arg-Gly-Asp (RGD) sequence found in the flexible beta G-beta H loop of the viral capsid protein VP1. The role of the RGD sequence in attachment of virus to cells was tested by using synthetic full-length viral RNAs mutated within or near the RGD sequence. Baby hamster kidney (BHK) cells transfected with three different RNAs carrying mutations bordering the RGD sequence produced infectious viruses with wild-type plaque morphology; however, one of these mutant viruses bound to cells less efficiently than wild type. BHK cells transfected with RNAs containing changes within the RGD sequence produced noninfectious particles indistinguishable from wild-type virus in terms of sedimentation coefficient, binding to monoclonal antibodies, and protein composition. These virus-like particles are defined as ads- viruses, since they were unable to adsorb to and infect BHK cells. These mutants were defective only in cell binding, since antibody-complexed ads- viruses were able to infect Chinese hamster ovary cells expressing an immunoglobulin Fc receptor. These results confirm the essential role of the RGD sequence in binding of foot-and-mouth disease virus to susceptible cells and demonstrate that the natural cellular receptor for the virus serves only to bind virus to the cell.
口蹄疫病毒似乎通过与病毒衣壳蛋白VP1的柔性βG-βH环中发现的精氨酸-甘氨酸-天冬氨酸（RGD）序列处的细胞结合来引发感染。通过使用在RGD序列内或其附近发生突变的合成全长病毒RNA，测试了RGD序列在病毒与细胞附着中的作用。用携带与RGD序列相邻突变的三种不同RNA转染的幼仓鼠肾（BHK）细胞产生了具有野生型蚀斑形态的传染性病毒；然而，这些突变病毒之一与细胞的结合效率低于野生型。用含有RGD序列内变化的RNA转染的BHK细胞产生了在沉降系数、与单克隆抗体的结合以及蛋白质组成方面与野生型病毒无法区分的非传染性颗粒。这些病毒样颗粒被定义为吸附缺陷型病毒（ads-病毒），因为它们无法吸附并感染BHK细胞。这些突变体仅在细胞结合方面存在缺陷，因为抗体复合的吸附缺陷型病毒能够感染表达免疫球蛋白Fc受体的中国仓鼠卵巢细胞。这些结果证实了RGD序列在口蹄疫病毒与易感细胞结合中的重要作用，并表明该病毒的天然细胞受体仅用于将病毒与细胞结合。
