Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60516, USA.
J Gen Virol. 2010 Sep;91(Pt 9):2197-202. doi: 10.1099/vir.0.021444-0. Epub 2010 May 19.
In cell lines, the Epstein-Barr virus (EBV)-encoded protein latent membrane protein 2A (LMP2A) protects B-cells from apoptosis by blocking B-cell receptor (BCR) signalling. However, EBV-infected B-cells in vivo are extremely different from cell lines. This study used a murine transgenic model in which B-cells express LMP2A and a BCR specific for hen egg lysozyme to determine whether LMP2A protects resting and antigen-activated B-cells from apoptosis. LMP2A allows BCR signal transduction and induces constitutive activation of NF-kappaB to increase Bcl-2 levels that afford LMP2A-mediated protection from apoptosis in the absence or presence of antigen. In contrast, low levels of NF-kappaB inhibitor only affected Bcl-2 and Bcl-xL levels and increased apoptosis in LMP2A-negative B-cells after BCR cross-linking. These data suggest that LMP2A uniquely makes resting B-cells sensitive to NF-kappaB inhibition and apoptosis and suggest that NF-kappaB may be a novel target to eradicate latently EBV-infected B-cells.
在细胞系中，EB 病毒（EBV）编码的潜伏膜蛋白 2A（LMP2A）通过阻断 B 细胞受体（BCR）信号来保护 B 细胞免于凋亡。然而，体内感染 EBV 的 B 细胞与细胞系极为不同。本研究使用了一种小鼠转基因模型，其中 B 细胞表达 LMP2A 和针对鸡卵溶菌酶的 BCR，以确定 LMP2A 是否保护静止和抗原激活的 B 细胞免于凋亡。LMP2A 允许 BCR 信号转导，并诱导 NF-κB 的组成性激活，从而增加 Bcl-2 水平，从而在不存在或存在抗原的情况下提供 LMP2A 介导的抗凋亡保护。相比之下，低水平的 NF-κB 抑制剂仅影响 Bcl-2 和 Bcl-xL 水平，并在 BCR 交联后增加 LMP2A 阴性 B 细胞的凋亡。这些数据表明，LMP2A 使静止的 B 细胞对 NF-κB 抑制和凋亡敏感，并且表明 NF-κB 可能是根除潜伏性 EBV 感染 B 细胞的新靶点。
