Raab-Traub Nancy
Department of Microbiology, Lineberger Comprehensive Cancer Center, CB#7295, University of North Carolina, Chapel Hill, NC, 27599-7295, USA.
Curr Top Microbiol Immunol. 2015;390(Pt 1):339-63. doi: 10.1007/978-3-319-22822-8_14.
The Epstein-Barr herpesvirus (EBV) is an important human pathogen that is closely linked to several major malignancies including the major epithelial tumor, undifferentiated nasopharyngeal carcinoma (NPC). This important tumor occurs with elevated incidence in specific areas, particularly in southern China but also in Mediterranean Africa and some regions of the Middle East. Regardless of tumor prevalence, undifferentiated NPC is consistently associated with EBV. The consistent detection of EBV in all cases of NPC, the maintenance of the viral genome in every cell, and the continued expression of viral gene products suggest that EBV is a necessary factor for the malignant growth in vivo. However, the molecular characterization of the infection and identification of critical events have been hampered by the difficulty in developing in vitro models of NPC. Epithelial cell infection is difficult in vitro and in contrast to B-cell infection does not result in immortalization and transformation. Cell lines established from NPC usually do not retain the genome, and the successful establishment of tumor xenografts is difficult. However, critical genetic changes that contribute to the onset and progression of NPC and key molecular properties of the viral genes expressed in NPC have been identified. In some cases, viral expression becomes increasingly restricted during tumor progression and tumor cells may express only the viral nuclear antigen EBNA1 and viral noncoding RNAs. As NPC develops in the immunocompetent, the continued progression of deregulated growth likely reflects the combination of expression of viral oncogenes in some cells and viral noncoding RNAs that likely function synergistically with changes in cellular RNA and miRNA expression.
爱泼斯坦-巴尔疱疹病毒（EBV）是一种重要的人类病原体，与多种主要恶性肿瘤密切相关，包括主要的上皮性肿瘤——未分化鼻咽癌（NPC）。这种重要的肿瘤在特定地区发病率较高，特别是在中国南方，但在地中海非洲和中东的一些地区也有发生。无论肿瘤的流行情况如何，未分化鼻咽癌始终与EBV相关。在所有鼻咽癌病例中都能持续检测到EBV，病毒基因组在每个细胞中得以维持，并且病毒基因产物持续表达，这表明EBV是体内恶性生长的必要因素。然而，由于难以建立鼻咽癌的体外模型，感染的分子特征和关键事件的鉴定受到了阻碍。体外上皮细胞感染困难，与B细胞感染不同，上皮细胞感染不会导致永生化和转化。从鼻咽癌建立的细胞系通常不会保留基因组，并且成功建立肿瘤异种移植也很困难。然而，已经确定了导致鼻咽癌发生和进展的关键基因变化以及鼻咽癌中表达的病毒基因的关键分子特性。在某些情况下，病毒表达在肿瘤进展过程中变得越来越受限，肿瘤细胞可能仅表达病毒核抗原EBNA1和病毒非编码RNA。由于鼻咽癌在免疫功能正常的个体中发生，生长失调的持续进展可能反映了某些细胞中病毒癌基因的表达与病毒非编码RNA的组合，这些病毒非编码RNA可能与细胞RNA和miRNA表达的变化协同发挥作用。
