Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry
Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry
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DOI：
10.1128/jvi.72.9.7064-7074.1998
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发表时间：
1998-09-01
影响因子：
5.4
通讯作者：
Eisenberg, RJ
中科院分区：
文献类型：
--
作者：
Krummenacher, C;Nicola, AV;Eisenberg, RJ
几种细胞膜蛋白已被鉴定为单纯疱疹病毒（HSV）进入介质（Hve）。HveA（以前称为HVEM）是肿瘤坏死因子受体家族的成员，而脊髓灰质炎病毒受体相关蛋白1和2（PRR 1和PRR 2，重命名为HveC和HveB）属于免疫球蛋白超家族。在这里，我们表明，截短形式的HveC直接结合到HSV糖蛋白D（gD）在溶液中，并在病毒粒子的表面。这种相互作用依赖于go的天然构象，但不依赖于其N-连接的糖基化。可溶性go和HveC之间的复合物形成似乎涉及一种HveC蛋白的一个或两个go分子。由于HveA也通过与go相互作用介导HSV进入，我们比较了两种结构上不相关的受体与go的结合。几个去变体的分析表明，结构和访问的N-末端结构域的去，HveA的结合是必不可少的，是没有必要的HveC的相互作用。GO功能区II、III和IV中的突变对HveC或HveA的结合具有相似的影响。用中和性抗go单克隆抗体（MAb）进行的竞争测定显示，来自Tt组的MAb阻止HveC和HveA与病毒体结合。然而，Ia组单克隆抗体阻断HveC结合，但不阻断HveA结合，相反，VII组单克隆抗体阻断HveA结合，但不阻断HveC结合。因此，我们提出HSV进入可以通过两个结构上不相关的GO受体通过与gD相关但不相同的结合来介导。
Several cell membrane proteins have been identified as herpes simplex virus (HSV) entry mediators (Hve). HveA (formerly HVEM) is a member of the tumor necrosis factor receptor family, whereas the poliovirus receptor-related proteins 1 and 2 (PRR1 and PRR2, renamed HveC and HveB) belong to the immunoglobulin superfamily. Here we show that a truncated form of HveC directly binds to HSV glycoprotein D (gD) in solution and at the surface of virions. This interaction is dependent on the native conformation of go but independent of its N-linked glycosylation. Complex formation between soluble go and HveC appears to involve one or two go molecules for one HveC protein. Since HveA also mediates HSV entry by interacting with go, we compared both structurally unrelated receptors for their binding to go. Analyses of several go variants indicated that structure and accessibility of the N-terminal domain of go, essential for HveA binding, was not necessary for HveC interaction. Mutations in functional regions II, III, and IV of go had similar effects on binding to either HveC or HveA. Competition assays with neutralizing anti-go monoclonal antibodies (MAbs) showed that MAbs from group Tt, prevented HveC and HveA binding to virions. However, group Ia MAbs blocked HveC but not HveA binding, and conversely, group VII MAbs blocked HveA but not HveC binding. Thus, we propose that HSV entry can be mediated by two structurally unrelated go receptors through related but not identical binding with gD.