为了探讨EB病毒潜伏性膜蛋白1（LMP1）促原代小鼠胚胎成纤维（MEF）细胞增殖规律及作用机制;构建包含野生型LMP1和其TNFR相关死亡区（TRADD）结合区即羧基末端384～386氨基酸置换（YYD→ID）的突变型LMP1逆转录病毒;感染原代培养的MEF细胞;动态观察各细胞在传代培养过程中细胞动力学和形态学变化。发现对照细胞（MEF-LNSX）传至P8～P10时出现明显的生长阻滞;携突变型LMP1的细胞（MEF-LMP1TRADD）自P10起倍增时间逐渐延长; P19时出现明显生长阻滞;而携野生型LMP的细胞（MEF-LMP1）倍增时间逐渐降低并发生了永生化。Western blot检测发现MEF-LNSX细胞CyclinA表达自P4起明显降低;MEF-LMP1TRADD细胞自P10显著增高后快速降低;MEF-LMP1自P10显著增高后一直维持在较高水平。结果表明：LMP1能促进MEF细胞增殖并诱导体外永生;LMPTRADD则仅能诱导MEF细胞的早期增殖。提示羧基末端区（TRADD）是LMP1促MEF细胞永生的重要活性部位;上调CyclinA表达可能是其作用机制之一。

To investigate the action and mechanisms of Epstein Barr-virus(EBV) latent membrane protein1(LMP1) in stimulating the proliferation of primary mouse embryonic fibroblast (MEF) cells the retrovirus (RV) containing wild type LMP1(wt-LMP1) and mutant type LMP1(mt-LMP1);which replaced YYD with ID in tumor necrosis factor receptor associated death domain(TRADD)-binding site;were constructed and used to infect the MEF cells;respectively. Then cytokinetic and morphologic changes from infected cells at the course of passage were observed and found that control cells (MEF-LNSX) showed an apparent growth arrest from passages 8 (P8). In contrast;mt-LMP1 prolonged the cell (MEF-LMP1TRADD) doubling time since P10 and arrested growth at P19;while the MEF-LMP1 cell with wt-LMP1 had an accurate doubling time and displayed a immortalization. Meantime;the expression of cyclinA had a decrease in MEF-LNSX and MEF-LMP1TRADD after P4and P10 respectively. while in MEF-LMP1;cyclinA increased from P10 and kept at a high level. These results suggested that LMP1 can stimulate proliferation of MEF cells and induce their immortalization;while LMP1TRADD only induces an early proliferation of MEF cells. It is implied that TRADD domain might involve in LMP1-induced MEF cells immortalization.