Jackson T, Ellard F M, Ghazaleh R A, Brookes S M, Blakemore W E, Corteyn A H, Stuart D I, Newman J W, King A M
Pirbright Laboratory, Institute for Animal Health, Pirbright, Surrey, United Kingdom.
J Virol. 1996 Aug;70(8):5282-7. doi: 10.1128/JVI.70.8.5282-5287.1996.
Foot-and-mouth disease virus (FMDV) enters cells by attaching to cellular receptor molecules of the integrin family, one of which has been identified as the RGD-binding integrin alpha(v)beta3. Here we report that, in addition to an integrin binding site, type O strains of FMDV share with natural ligands of alpha(v)beta3 (i.e., vitronectin and fibronectin) a specific affinity for heparin and that binding to the cellular form of this sulfated glycan, heparan sulfate, is required for efficient infection of cells in culture. Binding of the virus to paraformaldehyde-fixed cells was powerfully inhibited by agents such as heparin, that compete with heparan sulfate or by agents that compete for heparan sulfate (platelet factor 4) or that inactivate it (heparinase). Neither chondroitin sulfate, a structurally related component of the extracellular matrix, nor dextran sulfate appreciably inhibited binding. The functional importance of heparan sulfate binding was demonstrated by the facts that (i) infection of live cells by FMDV could also be blocked specifically by heparin, albeit at a much higher concentration of inhibitor; (ii) pretreatment of cells with heparinase reduced the number of plaques formed compared with that for untreated cells; and (iii) mutant cell lines deficient in heparan sulfate expression were unable to support plaque formation by FMDV, even though they remained equally susceptible to another picornavirus, bovine enterovirus. The results show that entry of type O FMDV into cells is a complex process and suggest that the initial contact with the cell surface is made through heparan sulfate.
口蹄疫病毒（FMDV）通过附着于整合素家族的细胞受体分子进入细胞，其中一种已被鉴定为RGD结合整合素α(v)β3。在此我们报告，除了整合素结合位点外，O型口蹄疫病毒株与α(v)β3的天然配体（即玻连蛋白和纤连蛋白）一样，对肝素具有特异性亲和力，并且与这种硫酸化聚糖的细胞形式硫酸乙酰肝素结合是在培养中有效感染细胞所必需的。病毒与多聚甲醛固定细胞的结合受到肝素等与硫酸乙酰肝素竞争的试剂、与硫酸乙酰肝素竞争的试剂（血小板因子4）或使其失活的试剂（肝素酶）的强烈抑制。细胞外基质的结构相关成分硫酸软骨素和硫酸葡聚糖均未明显抑制结合。硫酸乙酰肝素结合的功能重要性体现在以下事实：（i）FMDV对活细胞的感染也可被肝素特异性阻断，尽管所需抑制剂浓度要高得多；（ii）用肝素酶预处理细胞后，形成的噬斑数量比未处理细胞减少；（iii）缺乏硫酸乙酰肝素表达的突变细胞系无法支持FMDV形成噬斑，尽管它们对另一种小RNA病毒牛肠道病毒仍同样敏感。结果表明，O型FMDV进入细胞是一个复杂的过程，并提示与细胞表面的初始接触是通过硫酸乙酰肝素进行的。
