期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：48
页码：20464-20469
DOI：10.1073/pnas.0907508106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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{beta}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.
