Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus
Junctional adhesion molecule a serves as a receptor for prototype and field-isolate strains of mammalian reovirus
复制标题
DOI：
10.1128/jvi.79.13.7967-7978.2005
复制
发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Dermody, TS
中科院分区：
文献类型：
--
作者：
Campbell, JA;Schelling, P;Dermody, TS
呼肠孤病毒感染是由病毒附着蛋白sigma 1与宿主细胞表面受体结合而引发的。sigma 1蛋白是一种细长的纤维，由插入病毒粒子的n端尾部和从病毒粒子表面伸出的c端头部组成。呼肠孤病毒原型株1型Lang/53 （T1L/53）和3型Dearing/55 （T3D/55）使用连接粘附分子A （JAM-A）作为受体。T3D/55 sigma 1蛋白的c端一半直接与JAM-A相互作用，但尚未确定受体结合特异性的决定因素。在这项研究中，我们研究了JAM-A是否也介导了原型呼肠孤病毒2型Jones/55 （T2J/55）和一组代表三种血清型的现场分离株的附着。JAM-A特异性抗体能够抑制T1L/53、T2J/55和T3D/55对HeLa细胞的感染，这表明所有三种血清型菌株都使用JAM-A作为受体。为了证实这些发现，我们将JAM- a或结构相关的JAM家族成员JAM- b和JAM- c引入中国仓鼠卵巢细胞，这些细胞对呼肠孤病毒感染的许可性很差。原型和野分离呼肠孤病毒株都能感染转染JAM-A的细胞，而不能感染转染JAM-B或JAM-C的细胞。对所选菌株编码sigma 1的SI基因片段的序列分析显示，所推断的sigma 1氨基酸序列在三种血清型之间几乎没有保守性。这与在每种血清型中观察到的序列变异性形成鲜明对比，这仅限于少数氨基酸。将这些残基映射到sigma 1的晶体结构上，确定了守恒和可变性区域，表明JAM-A可能通过sigma 1头部结构域底部的保守表面结合。
Reovirus infectious are initiated by the binding of viral attachment protein sigma 1 to receptors on the surface of host cells. The sigma 1 protein is an elongated fiber comprised of an N-terminal tail that inserts into the virion and a C-terminal head that extends from the virion surface. The prototype reovirus strains type 1 Lang/53 (T1L/53) and type 3 Dearing/55 (T3D/55) use junctional adhesion molecule A (JAM-A) as a receptor. The C-terminal half of the T3D/55 sigma 1 protein interacts directly with JAM-A, but the determinants of receptor-binding specificity have not been identified. In this study, we investigated whether JAM-A also mediates the attachment of the prototype reovirus strain type 2 Jones/55 (T2J/55) and a panel of field-isolate strains representing each of the three serotypes. Antibodies specific for JAM-A were capable of inhibiting infections of HeLa cells by T1L/53, T2J/55, and T3D/55, demonstrating that strains of all three serotypes use JAM-A as a receptor. To corroborate these findings, we introduced JAM-A or the structurally related JAM family members JAM-B and JAM-C into Chinese hamster ovary cells, which are poorly permissive for reovirus infection. Both prototype and field-isolate reovirus strains were capable of infecting cells transfected with JAM-A but not those transfected with JAM-B or JAM-C. A sequence analysis of the sigma 1-encoding SI gene segment of the strains chosen for study revealed little conservation in the deduced sigma 1 amino acid sequences among the three serotypes. This contrasts markedly with the observed sequence variability within each serotype, which is confined to a small number of amino acids. Mapping of these residues onto the crystal structure of sigma 1 identified regions of conservation and variability, suggesting a likely mode of JAM-A binding via a conserved surface at the base of the sigma 1 head domain.