Replication of Epstein-Barr Viral DNA

Replication of Epstein-Barr Viral DNA
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DOI:
10.1101/cshperspect.a013029
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发表时间:
2013-01-01
影响因子:
7.2
通讯作者:
Sugden, Bill
Sugden, Bill
中科院分区:
生物学1区
文献类型:
--
作者:
Hammerschmidt, Wolfgang;Sugden, Bill

文献摘要

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EB病毒(EBV)是人类肿瘤病毒的范例:它是第一种被认为会导致人类癌症的病毒;它会导致淋巴瘤和癌症;但这些肿瘤很少出现,因为世界上大多数人都感染了这种病毒。EBV在受感染的正常和肿瘤细胞中维持在染色体外。这些病毒质粒中有84%复制每个S期,获得许可,需要单个病毒蛋白进行合成,并且可以使用两个功能不同的DNA复制起点,oriP和Raji ori。88%的新合成质粒被忠实地分离到子细胞中。感染性病毒颗粒在这些潜伏感染的条件下不会合成。这种质粒复制与EBV宿主细胞的存活一致。感染群体中的稀有细胞自发地或在外源诱导后支持EBV的裂解周期,这对细胞是致命的。在这种情况下,病毒DNA复制100倍或更多,使用第三种病毒DNA复制起点oriLyt和许多病毒蛋白。在这里,我们将描述三种模式的EB病毒的复制作为一个功能的病毒的起源和病毒和细胞蛋白质,介导的DNA合成从这些起源集中,在可行的情况下,在我们的理解的最新进展。
Epstein-Barr virus (EBV) is a paradigm for human tumor viruses: it is the first virus recognized to cause cancer in people; it causes both lymphomas and carcinomas; yet these tumors arise infrequently given that most people in the world are infected with the virus. EBV is maintained extrachromosomally in infected normal and tumor cells. Eighty-four percent of these viral plasmids replicate each S phase, are licensed, require a single viral protein for their synthesis, and can use two functionally distinct origins of DNA replication, oriP, and Raji ori. Eighty-eight percent of newly synthesized plasmids are segregated faithfully to the daughter cells. Infectious viral particles are not synthesized under these conditions of latent infection. This plasmid replication is consistent with survival of EBV's host cells. Rare cells in an infected population either spontaneously or following exogenous induction support EBV's lytic cycle, which is lethal for the cell. In this case, the viral DNA replicates 100-fold or more, uses a third kind of viral origin of DNA replication, oriLyt, and many viral proteins. Here we shall describe the three modes of EBV's replication as a function of the viral origins used and the viral and cellular proteins that mediate the DNA synthesis from these origins focusing, where practical, on recent advances in our understanding.