Rosemarie Quincy, Sugden Bill
Department of Oncology, McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Microorganisms. 2020 Nov 19;8(11):1824. doi: 10.3390/microorganisms8111824.
Epstein-Barr Virus (EBV) contributes to the development of lymphoid and epithelial malignancies. While EBV's latent phase is more commonly associated with EBV-associated malignancies, there is increasing evidence that EBV's lytic phase plays a role in EBV-mediated oncogenesis. The lytic phase contributes to oncogenesis primarily in two ways: (1) the production of infectious particles to infect more cells, and (2) the regulation of cellular oncogenic pathways, both cell autonomously and non-cell autonomously. The production of infectious particles requires the completion of the lytic phase. However, the regulation of cellular oncogenic pathways can be mediated by an incomplete (abortive) lytic phase, in which early lytic gene products contribute substantially, whereas late lytic products are largely dispensable. In this review, we discuss the evidence of EBV's lytic phase contributing to oncogenesis and the role it plays in tumor formation and progression, as well as summarize known mechanisms by which EBV lytic products regulate oncogenic pathways. Understanding the contribution of EBV's lytic phase to oncogenesis will help design ways to target it to treat EBV-associated malignancies.
爱泼斯坦-巴尔病毒(EBV)与淋巴和上皮恶性肿瘤的发生发展有关。虽然EBV的潜伏期更常与EBV相关的恶性肿瘤相关,但越来越多的证据表明,EBV的裂解期在EBV介导的肿瘤发生中起作用。裂解期主要通过两种方式促进肿瘤发生:(1)产生感染性颗粒以感染更多细胞;(2)细胞自主和非细胞自主地调节细胞致癌途径。感染性颗粒的产生需要裂解期的完成。然而,细胞致癌途径的调节可由不完全(流产性)裂解期介导,其中早期裂解基因产物起主要作用,而晚期裂解产物在很大程度上是可有可无的。在本综述中,我们讨论了EBV裂解期促进肿瘤发生的证据及其在肿瘤形成和进展中所起的作用,并总结了EBV裂解产物调节致癌途径的已知机制。了解EBV裂解期对肿瘤发生的作用将有助于设计针对它的方法来治疗EBV相关的恶性肿瘤。