Barton E S, Forrest J C, Connolly J L, Chappell J D, Liu Y, Schnell F J, Nusrat A, Parkos C A, Dermody T S
Department of Microbiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Cell. 2001 Feb 9;104(3):441-51. doi: 10.1016/s0092-8674(01)00231-8.
Virus attachment to cells plays an essential role in viral tropism and disease. Reovirus serotypes 1 and 3 differ in the capacity to target distinct cell types in the murine nervous system and in the efficiency to induce apoptosis. The binding of viral attachment protein sigma1 to unidentified receptors controls these phenotypes. We used expression cloning to identify junction adhesion molecule (JAM), an integral tight junction protein, as a reovirus receptor. JAM binds directly to sigma1 and permits reovirus infection of nonpermissive cells. Ligation of JAM is required for reovirus-induced activation of NF-kappaB and apoptosis. Thus, reovirus interaction with cell-surface receptors is a critical determinant of both cell-type specific tropism and virus-induced intracellular signaling events that culminate in cell death.
病毒与细胞的附着在病毒嗜性和疾病中起着至关重要的作用。呼肠孤病毒1型和3型在靶向小鼠神经系统中不同细胞类型的能力以及诱导细胞凋亡的效率方面存在差异。病毒附着蛋白sigma1与未鉴定受体的结合控制着这些表型。我们利用表达克隆技术鉴定出连接黏附分子(JAM),一种完整的紧密连接蛋白,作为呼肠孤病毒的受体。JAM直接与sigma1结合,并允许呼肠孤病毒感染非允许细胞。JAM的连接是呼肠孤病毒诱导的NF-κB激活和细胞凋亡所必需的。因此,呼肠孤病毒与细胞表面受体的相互作用是细胞类型特异性嗜性和最终导致细胞死亡的病毒诱导细胞内信号事件的关键决定因素。