Ayee Richmond, Ofori Maame Ekua Oforiwaa, Wright Edward, Quaye Osbourne
Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana.
West African Center for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra, Ghana.
J Cancer. 2020 Jan 17;11(7):1737-1750. doi: 10.7150/jca.37282. eCollection 2020.
Epstein Barr virus (EBV) is a cosmopolitan oncogenic virus, infecting about 90% of the world's population and it is associated to tumors originating from both epithelia and hematopoietic cells. Transmission of the virus is mainly through oral secretions; however, transmission through organ transplantation and blood transfusion has been reported. In order to evade immune recognition, EBV establishes latent infection in B lymphocytes where it expresses limited sets of proteins called EBV transcription programs (ETPs), including six nuclear antigens (EBNAs), three latent membrane proteins (LMP), and untranslated RNA called EBV encoded RNA (EBER), shown to efficiently transform B cells into lymphoblastic cells. These programs undergo different patterns of expression which determine the occurrence of distinct types of latency in the pathogenesis of a particular tumor. Hematopoietic cell derived tumors include but not limited to Burkitt's lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and natural killer (NK)/T cell lymphoma. EBV undergoes lytic infection in epithelia cells for amplification of the viral particle for transmission where it expresses lytic stage genes. However, for reasons yet to be unveiled, EBV switches from the expression of lytic stage genes to the expression of ETPs in epithelia cells. The expression of the ETPs lead to the transformation of epithelia cells into permanently proliferating cells, resulting in epithelia cell derived malignancies such as nasopharyngeal cancer, gastric cancer, and breast cancer. In this review, we have summarized the current updates on EBV associated epithelial and B cell-derived malignancies, and the role of EBV latency gene products in the pathogenesis of the cancers, and have suggested areas for future studies when considering therapeutic measures.
爱泼斯坦-巴尔病毒(EBV)是一种世界性的致癌病毒,感染了全球约90%的人口,它与起源于上皮细胞和造血细胞的肿瘤有关。该病毒主要通过口腔分泌物传播;然而,也有通过器官移植和输血传播的报道。为了逃避免疫识别,EBV在B淋巴细胞中建立潜伏感染,在那里它表达有限的一组蛋白质,称为EBV转录程序(ETPs),包括六种核抗原(EBNAs)、三种潜伏膜蛋白(LMPs)以及一种名为EBV编码RNA(EBER)的非翻译RNA,这些已被证明能有效地将B细胞转化为淋巴母细胞。这些程序经历不同的表达模式,这决定了特定肿瘤发病机制中不同类型潜伏的发生。造血细胞来源的肿瘤包括但不限于伯基特淋巴瘤、霍奇金淋巴瘤、移植后淋巴细胞增生性疾病以及自然杀伤(NK)/T细胞淋巴瘤。EBV在上皮细胞中进行裂解感染以扩增病毒颗粒用于传播,在那里它表达裂解阶段基因。然而,由于尚未揭示的原因,EBV在上皮细胞中从裂解阶段基因的表达切换到ETPs的表达。ETPs的表达导致上皮细胞转化为永久增殖细胞,从而导致上皮细胞来源的恶性肿瘤,如鼻咽癌、胃癌和乳腺癌。在这篇综述中,我们总结了关于EBV相关上皮和B细胞来源恶性肿瘤的最新进展,以及EBV潜伏基因产物在癌症发病机制中的作用,并提出了在考虑治疗措施时未来研究的方向。