Maier Sabine, Staffler Gabriele, Hartmann Andrea, Höck Julia, Henning Karen, Grabusic Kristina, Mailhammer Reinhard, Hoffmann Reinhard, Wilmanns Matthias, Lang Roland, Mages Jörg, Kempkes Bettina
GSF-National Research Center for Environment and Health, Institute of Clinical Molecular Biology, Munich, Germany.
J Virol. 2006 Oct;80(19):9761-71. doi: 10.1128/JVI.00665-06.
Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key determinant in the EBV-driven B-cell growth transformation process. By activating an array of viral and cellular target genes, EBNA-2 initiates a cascade of events which ultimately cause cell cycle entry and the proliferation of the infected B cell. In order to identify cellular target genes that respond to EBNA-2 in the absence of other viral factors, we have performed a comprehensive search for EBNA-2 target genes in two EBV-negative B-cell lines. This screen identified 311 EBNA-2-induced and 239 EBNA-2-repressed genes that were significantly regulated in either one or both cell lines. The activation of most of these genes had not previously been attributed to EBNA-2 function and will be relevant for the identification of EBNA-2-specific contributions to EBV-associated malignancies. The diverse spectrum of EBNA-2 target genes described in this study reflects the broad spectrum of EBNA-2 functions involved in virus-host interactions, including cell signaling molecules, adapters, genes involved in cell cycle regulation, and chemokines.
爱泼斯坦-巴尔病毒（EBV）核抗原2（EBNA-2）是EBV驱动的B细胞生长转化过程中的关键决定因素。通过激活一系列病毒和细胞靶基因，EBNA-2引发一连串事件，最终导致细胞进入细胞周期并使受感染的B细胞增殖。为了在没有其他病毒因子的情况下鉴定对EBNA-2有反应的细胞靶基因，我们在两种EBV阴性B细胞系中对EBNA-2靶基因进行了全面搜索。该筛选鉴定出311个EBNA-2诱导基因和239个EBNA-2抑制基因，这些基因在其中一种或两种细胞系中受到显著调控。这些基因中的大多数此前并未被认为与EBNA-2功能有关，它们对于确定EBNA-2对EBV相关恶性肿瘤的特异性作用具有重要意义。本研究中描述的EBNA-2靶基因的多样谱反映了EBNA-2在病毒-宿主相互作用中涉及的广泛功能，包括细胞信号分子、衔接蛋白、参与细胞周期调控的基因以及趋化因子。
