病毒受体结合位点与细胞表面受体结合是启动口蹄疫病毒（FMDV）感染的第一步，决定着病毒感染细胞类型、致病性和宿主嗜性等。前期研究发现，Asia1型FMDV的受体结合位点RGD突变成了RSD或RDD，致其对乳鼠、牛和猪三种宿主都发生较大的致病性差异和宿主嗜性变异。为了阐明RGD突变致其宿主嗜性变异的受体路径，本研究用反向遗传技术制备的含RGD、RSD和RDD基序的毒株平行感染同一宿主的各个单受体（αvβ3、αvβ6、αvβ1、αvβ8和HS）细胞系及整联蛋白与HS受体双阴性细胞系，比较测定这些病毒与受体结合、侵入和复制情况，进一步确定这些毒株生物学特性（PFU、TCID50和病毒复制动力曲线等）的差异，鉴定RGD基序突变株对受体路径的识别和差异。并从宿主的角度，比较研究牛和猪的受体路径对FMDV感染性的影响。为进一步鉴定FMDV第三未知受体和阐明"FMDV宿主嗜性变异"的科学问题奠定基础。

The interaction between virus and its cellular receptor initiates a chain of dynamic events that will enable entry of the virus into the cell. In previous studies, we found that two foot and mouth disease viruses harbored alternative receptor binding sites (Arg-Asp-Asp (RDD) or Arg-Ser-Asp (RSD)) instead of the Arg-Gly-Asp (RGD) integrin recognition motif. Using reverse genetics technique, the RDD-, RSD-, and RGD-containing FMD viruses were rescued, and the data showed different pathogenicity and host tropism in mouse, swine and bovine. The objective of this study is to determine what is the molecular basis underlying the virulence and host tropism of FMD viruses, and how the non-RGD FMD viruses recognize the receptor-mediated pathways. These virus-receptor interactions that will provide links to virus tropism and pathogenesis. To achieve: (1) stable cell lines expressing αvβ3，αvβ6，αvβ1 and αvβ8 from mouse, swine and bovine will be established. (2) These established cell lines and the cells only expressed heparan sulfate (HS) will be infected by the above-mentioned FMD viruses and the molecular biological characteristics including plaque forming units (PFU), 50% tissue culture infectious dose (TCID50) and viral replication kinetic curve will be examined and analyzed.（3）The pgsD-677(a CHO cell mutant deficient for heparan sulfate polymerization)will be infected and analyzed by non-RGD FMD viruses.(4) The cell lines expressing different host receptors such as αvβ3，αvβ6，αvβ1, αvβ8 or HS will be infected by same strain. The above-mentioned molecular biological characteristics will be measured. The results will be useful as the molecular basis underlying the virulence and host tropism of the foot-and-mouth disease viruses.