Tsao Sai Wah, Tsang Chi Man, Lo Kwok Wai
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR.
Philos Trans R Soc Lond B Biol Sci. 2017 Oct 19;372(1732). doi: 10.1098/rstb.2016.0270.
Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'.
爱泼斯坦-巴尔病毒(EBV)与多种人类癌症相关,包括淋巴癌和上皮癌。在未分化鼻咽癌(NPC)中可见与EBV感染的最密切关联,这种癌症在中国南方人群中呈地方性流行。已确定NPC风险与6号染色体p臂上的HLA基因座之间存在强关联,这表明EBV抗原呈递给宿主免疫细胞与NPC风险之间存在联系。NPC中的EBV感染起源于克隆性,强烈提示NPC由单个EBV感染细胞的克隆性扩增发展而来。在上皮细胞中,EBV感染的默认程序是裂解复制。然而,潜伏感染是NPC中EBV感染的主要模式。在侵袭前的鼻咽上皮中建立潜伏性EBV感染被认为是NPC发病机制的早期阶段。最近对NPC的基因组研究已在NF-κB信号传导的上游负调节因子中鉴定出多个体细胞突变。NF-κB信号传导失调可能有助于在NPC中建立潜伏性EBV感染。稳定的EBV感染和潜伏性EBV基因的表达被假定通过多种途径驱动侵袭前鼻咽上皮细胞向癌细胞的转化。本文是主题为“人类致癌病毒”的特刊的一部分。