Epstein-Barr virus Latent Membrane Protein 2A (LMP2A)-mediated changes in Fas expression and Fas-dependent apoptosis: Role of Lyn/Syk activation.
Epstein-Barr virus Latent Membrane Protein 2A (LMP2A)-mediated changes in Fas expression and Fas-dependent apoptosis: Role of Lyn/Syk activation.
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DOI：
10.1016/j.cellimm.2015.08.001
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发表时间：
2015-10
影响因子：
4.3
通讯作者：
Swanson-Mungerson M
中科院分区：
文献类型：
--
作者：
Incrocci R;Hussain S;Stone A;Bieging K;Alt LA;Fay MJ;Swanson-Mungerson M
EB病毒潜伏膜蛋白2A（LMP 2A）在EBV感染的B细胞的生发中心表达，生发中心是由活化的B细胞上的Fas参与诱导的显著凋亡的位点。来自B细胞受体（BCR）的信号保护生殖中心B细胞免于Fas介导的凋亡，并且由于LMP 2A是BCR模拟物，我们假设LMP 2A也将保护B细胞免于Fas介导的凋亡。令人惊讶的是，表达LMP 2A的潜伏感染的人和鼠B细胞系对Fas介导的凋亡更敏感，这通过Annexin-V染色的增加以及caspase-8，−3和PARP的裂解来确定。另外的研究表明，由于Fas表达的LMP 2A依赖性增强，表达LMP 2A的B细胞系表现出对Fas介导的凋亡的敏感性的林恩和Syk依赖性增加。这些发现表明LMP 2A直接增加促凋亡分子的能力，并对EBV潜伏期以及EBV相关恶性肿瘤的治疗具有意义。
Epstein-Barr virus Latent Membrane Protein 2A (LMP2A) is expressed in EBV-infected B cells in the germinal center, a site of significant apoptosis induced by engagement of Fas on activated B cells. Signals from the B cell receptor (BCR) protect germinal center B cells from Fas-mediated apoptosis, and since LMP2A is a BCR mimic, we hypothesized that LMP2A would also protect B cells from Fas-mediated apoptosis. Surprisingly, latently-infected human and murine B cell lines expressing LMP2A were more sensitive to Fas-mediated apoptosis, as determined by increases in Annexin-V staining, and cleavage of caspase-8, −3 and PARP. Additional studies show that LMP2A-expressing B cell lines demonstrate a Lyn- and Syk-dependent increase in sensitivity to Fas-mediated apoptosis, due to an LMP2A-dependent enhancement in Fas expression. These findings demonstrate the ability for LMP2A to directly increase a pro-apoptotic molecule and have implications for EBV latency as well as the treatment of EBV-associated malignancies.