Lucchesi Walter, Brady Gareth, Dittrich-Breiholz Oliver, Kracht Michael, Russ Rainer, Farrell Paul J
Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
J Virol. 2008 Aug;82(15):7456-66. doi: 10.1128/JVI.00223-08. Epub 2008 May 14.
A transfection assay with a lymphoblastoid cell line infected with Epstein-Barr virus was used to compare the abilities of type 1 and type 2 EBNA2 to sustain cell proliferation. The reduced proliferation in cells expressing type 2 EBNA2 correlated with loss of expression of some cell genes that are known to be targets of type 1 EBNA2. Microarray analysis of EBNA2 target genes identified a small number of genes that are more strongly induced by type 1 than by type 2 EBNA2, and one of these genes (CXCR7) was shown to be required for proliferation of lymphoblastoid cell lines. The Epstein-Barr virus LMP1 gene was also more strongly induced by type 1 EBNA2 than by type 2, but this effect was transient. Type 1 and type 2 EBNA2 were equally effective at arresting cell proliferation of Burkitt's lymphoma cell lines lacking Epstein-Barr virus and were also shown to cause apoptosis in these cells. The results indicate that differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2 may be the basis for the much weaker B-cell transformation activity of type 2 Epstein-Barr virus strains compared to type 1 strains.
利用感染了爱泼斯坦 - 巴尔病毒的淋巴母细胞系进行转染试验,以比较1型和2型EBNA2维持细胞增殖的能力。表达2型EBNA2的细胞中增殖减少与一些已知为1型EBNA2靶标的细胞基因表达缺失相关。对EBNA2靶基因的微阵列分析确定了少数基因,1型EBNA2对其诱导作用比2型更强,其中一个基因(CXCR7)被证明是淋巴母细胞系增殖所必需的。爱泼斯坦 - 巴尔病毒LMP1基因也受到1型EBNA2的诱导作用比2型更强,但这种效应是短暂的。1型和2型EBNA2在抑制缺乏爱泼斯坦 - 巴尔病毒的伯基特淋巴瘤细胞系的细胞增殖方面同样有效,并且还显示会导致这些细胞凋亡。结果表明,1型和2型爱泼斯坦 - 巴尔病毒EBNA2的差异基因调控可能是2型爱泼斯坦 - 巴尔病毒株与1型株相比B细胞转化活性弱得多的基础。