Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins αvβ6 or αvβ8
Fusion of epithelial cells by Epstein-Barr virus proteins is triggered by binding of viral glycoproteins gHgL to integrins αvβ6 or αvβ8
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DOI：
10.1073/pnas.0907508106
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发表时间：
2009-12-01
影响因子：
11.1
通讯作者：
Hutt-Fletcher, Lindsey M.
中科院分区：
文献类型：
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作者：
Chesnokova, Liudmila S.;Nishimura, Stephen L.;Hutt-Fletcher, Lindsey M.
EB病毒（EBV）是一种普遍存在的人类疱疹病毒，与淋巴和上皮肿瘤的发生有因果关系。病毒的进入需要病毒包膜和细胞膜的融合。与B淋巴细胞的融合需要病毒糖蛋白gB和糖蛋白的3部分复合物gHgLgp 42。它是由糖蛋白42（gp42）和HLA II类之间的相互作用触发的。然而，与上皮细胞的融合受到gp42的阻碍，而是由未知的上皮蛋白和gHgL的2部分复合物之间的相互作用触发。我们在这里报告说，gHgL结合与上皮细胞的亲和力高，结合的亲和力增加了3个数量级的Mn2+的存在下。结合和感染可以通过纤连蛋白和玻连蛋白、通过下调整合素α v或通过对应于包括KGDE基序的gH的13个氨基酸的肽来减少。表达gB和gHgL的细胞的融合可以被玻连蛋白阻断或通过添加可溶性截短的整合素α v β 6和α v α 8来触发。我们的结论是EBV gHgL和整合素α v β 6和α v β 8之间的直接相互作用可以为EBV与上皮细胞的融合提供触发。
Epstein-Barr, virus (EBV) is a ubiquitous human herpesvirus that is causally implicated in the development of lymphoid and epithelial tumors. Entry of virus requires fusion of virus envelopes and cell membranes. Fusion with B lymphocytes requires virus glycoprotein gB and a 3-part complex of glycoproteins, gHgLgp42. It is triggered by interactions between glycoprotein 42 (gp42) and HLA class II. However, fusion with epithelial cells is impeded by gp42 and instead is triggered by interactions between an unknown epithelial protein and a 2-part complex of gHgL. We report here that gHgL binds with high affinity to epithelial cells and that affinity of binding is increased by 3 orders of magnitude in the presence of Mn2+. Binding and infection can be reduced by fibronectin and vitronectin, by down-regulation of integrin alpha v, or by a peptide corresponding to 13 aa of gH which include a KGDE motif. Fusion of cells expressing gB and gHgL can be blocked by vitronectin or triggered by addition of soluble truncated integrins alpha v beta 6 and alpha v alpha 8. We conclude that the direct interaction between EBV gHgL and integrins alpha v beta 6 and alpha v beta 8 can provide the trigger for fusion of EBV with an epithelial cell.