Modeling early Epstein-Barr virus infection in Drosophila melanogaster:: The BZLF1 protein
Modeling early Epstein-Barr virus infection in Drosophila melanogaster:: The BZLF1 protein
复制标题
DOI：
10.1534/genetics.105.042572
复制
发表时间：
2005-11-01
期刊：
影响因子：
3.3
通讯作者：
LaJeunesse, DR
中科院分区：
文献类型：
--
作者：
Adamson, AL;Wright, N;LaJeunesse, DR
EB 病毒 (EBV) 是传染性单核细胞增多症的病原体，与多种癌症有关，包括淋巴瘤和鼻咽癌。 EBV 立即早期蛋白 BZLF1 作为 EBV 早期基因表达的转录激活剂，对于病毒在潜伏复制和裂解复制之间的转变至关重要。除了在 EBV 生命周期中发挥作用外，BZLF1 (Z) 还对宿主细胞环境产生深远影响，包括破坏细胞周期调节、信号转导途径和转录。为了了解 Z 与宿主细胞环境相互作用的性质，我们开发了早期 EBV 感染的果蝇模型，我们在果蝇眼睛中表达了 Z。使用该系统，我们鉴定了 Epstein-Barr 病毒 Z 蛋白和 shaven 之间高度保守的相互作用，shaven 是人类 Pax2/5/8 基因家族的果蝇同源物。 Pax5 是一种与 B 细胞发育有关的已知人类基因。 B 细胞特异性 Pax5 还促进 EBV Wp 启动子的 EBV 潜伏基因转录。我们的工作清楚地表明，果蝇系统是识别与人类感染性疾病相关的潜在遗传网络的适当且强大的工具。
Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and is associated with several forms of cancer, including lymphomas and nasopharyngeal carcinoma. The EBV immediate-early protein BZLF1 functions as a transcriptional activator of EBV early gene expression and is essential for the viral transition between latent and lytic replication. In addition to its role in the EBV life cycle, BZLF1 (Z) also has profound effects upon the host cellular environment, including disruption of cell cycle regulation, signal transduction pathways, and transcription. In an effort to understand the nature of Z interactions with the host cellular environment, we have developed a Drosophila model of early EBV infection, where we have expressed Z in the Drosophila eye. Using this system, we have identified a highly conserved interaction between the Epstein-Barr virus Z protein and shaven, a Drosophila homolog of the human Pax2/5/8 family of genes. Pax5 is a well-characterized human gene involved with B-cell development. The B-cell-specific Pax5 also promotes the transcription of EBV latent genes from the EBV Wp promoter. Our work clearly demonstrates that the Drosophila system is an appropriate and powerful tool for identifying the underlying genetic networks involved in human infections disease.