Wang D, Liebowitz D, Wang F, Gregory C, Rickinson A, Larson R, Springer T, Kieff E
Department of Medicine, Harvard University Medical School, Boston, Massachusetts 02115.
J Virol. 1988 Nov;62(11):4173-84. doi: 10.1128/JVI.62.11.4173-4184.1988.
A latent infection membrane protein (LMP) encoded by the Epstein-Barr virus (EBV) genome in latently infected, growth-transformed lymphocytes alters the phenotype of a human EBV-negative B-lymphoma cell line (Louckes) when introduced by gene transfer. These LMP-expressing cells exhibit increased homotypic adhesion due to increased expression of the adhesion molecules LFA-1 and ICAM-1. Increased homotypic adhesion could foster B-cell growth by facilitating autocrine growth factor effects. LFA-3 expression is also induced. The induction of LFA-3 and ICAM-1 results in increased heterotypic adhesion to T lymphocytes. This could result in more effective T-cell immune surveillance. Since LMP is expressed in EBV-transformed lymphocytes and has been demonstrated to transform rodent fibroblasts in vitro, a wide range of possible effects on B-lymphoma cell growth were assayed. In the Louckes B-lymphoma cell line, EBV LMP causes increased cell size, acid production, plasma membrane ruffling, and villous projections. Although cell proliferation rate was not greatly affected, the steady-state intracellular free calcium level, transforming growth factor beta responsiveness, and expression of the lymphocyte activation markers (CD23 and transferrin receptor) were increased. Thus, LMP appears to be a mediator of EBV effects on B-cell transformation. In transfected lymphoma cells, LMP localizes to patches at the cell periphery and associates with the cytoskeleton as it does in EBV-transformed B lymphocytes or in rodent fibroblasts. A partially deleted form of LMP (D1LMP) does not aggregate in patches or associate with the cytoskeleton and had little effect on B-cell growth. Thus, cytoskeletal association may be integral to LMP activity.
在潜伏感染、生长转化的淋巴细胞中，由爱泼斯坦-巴尔病毒（EBV）基因组编码的一种潜伏感染膜蛋白（LMP），通过基因转移导入人EBV阴性B淋巴瘤细胞系（Louckes）时，会改变其表型。这些表达LMP的细胞由于黏附分子LFA-1和ICAM-1表达增加而表现出同型黏附增强。同型黏附增强可通过促进自分泌生长因子效应来促进B细胞生长。LFA-3表达也被诱导。LFA-3和ICAM-1的诱导导致对T淋巴细胞的异型黏附增加。这可能导致更有效的T细胞免疫监视。由于LMP在EBV转化的淋巴细胞中表达，并且已被证明在体外可转化啮齿动物成纤维细胞，因此检测了其对B淋巴瘤细胞生长的一系列可能影响。在Louckes B淋巴瘤细胞系中，EBV LMP导致细胞大小增加、酸产生增加、质膜褶皱和绒毛状突起。虽然细胞增殖率没有受到很大影响，但稳态细胞内游离钙水平、转化生长因子β反应性以及淋巴细胞活化标志物（CD23和转铁蛋白受体）的表达均增加。因此，LMP似乎是EBV对B细胞转化作用的介质。在转染的淋巴瘤细胞中，LMP定位于细胞周边的斑块，并与细胞骨架相关联，就像在EBV转化的B淋巴细胞或啮齿动物成纤维细胞中一样。LMP的一种部分缺失形式（D1LMP）不会聚集形成斑块或与细胞骨架相关联，对B细胞生长几乎没有影响。因此，细胞骨架关联可能是LMP活性所必需的。
