Rechsteiner Markus P, Berger Christoph, Weber Matthias, Sigrist Jürg A, Nadal David, Bernasconi Michele
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
J Gen Virol. 2007 May;88(Pt 5):1454-1459. doi: 10.1099/vir.0.82790-0.
Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) blocks B-cell receptor (BCR) signalling after BCR cross-linking to inhibit activation of lytic EBV, and ectopically expressed LMP2B negatively regulates LMP2A. Here, it is demonstrated that silencing of LMP2B in EBV-harbouring Burkitt's lymphoma Akata cells results in reduced expression of EBV immediate-early lytic BZLF1 gene mRNA and late lytic gp350/220 protein upon BCR cross-linking. Similarly, reduction of lytic EBV activation was observed in Akata cells overexpressing LMP2A. In contrast, silencing of LMP2A expression resulted in higher lytic EBV mRNA and protein expression in BCR cross-linked Akata cells. These observations indicate a role for LMP2B distinct from that of LMP2A in regulation of lytic EBV activation in the host cell and support the hypothesis that LMP2B exhibits a negative-regulatory effect on the ability of LMP2A to maintain EBV latency by preventing the switch to lytic replication.
爱泼斯坦-巴尔病毒（EBV）潜伏膜蛋白2A（LMP2A）在B细胞受体（BCR）交联后阻断BCR信号传导，以抑制EBV裂解激活，而异位表达的LMP2B对LMP2A起负调节作用。在此，研究表明，在携带EBV的伯基特淋巴瘤Akata细胞中沉默LMP2B，会导致BCR交联后EBV立即早期裂解BZLF1基因mRNA和晚期裂解gp350/220蛋白的表达降低。同样，在过表达LMP2A的Akata细胞中也观察到裂解性EBV激活减少。相反，在BCR交联的Akata细胞中沉默LMP2A表达会导致更高的裂解性EBV mRNA和蛋白表达。这些观察结果表明，LMP2B在宿主细胞中调节裂解性EBV激活方面具有与LMP2A不同的作用，并支持以下假设：LMP2B通过防止向裂解复制的转变，对LMP2A维持EBV潜伏的能力表现出负调节作用。
