Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
Sci China Life Sci. 2012 Aug;55(8):735-43. doi: 10.1007/s11427-012-4362-3. Epub 2012 Aug 30.
Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections, such as Epstein-Barr virus. Epstein-Barr virus is a Γ-herpesvirus and is related to many malignant diseases, especially epithelial and lymph tumors. The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells. This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation. Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells. Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos. 5, 8, 9, and 10, particularly in sample No. 5. Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus. The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro. Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells, which may be involved in the anti-apoptosis activity of the infected cells. Confocal microscopy showed that pairs of molecules of cluster of differentiation 40, cluster of differentiation 40 ligand, and latent membrane protein 1 were colocalized on the surface of the infected cells. CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection. The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α. Anti-apoptosis and migration are known important biological characteristics of malignant cells. Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma. The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center, which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.
肝移植术后患者细胞免疫功能下降，易导致多种病毒感染，如 EBV（Epstein-Barr virus）。EBV 是一种γ疱疹病毒，与多种恶性疾病，尤其是上皮和淋巴肿瘤密切相关。CD40 与 CD40L 的异常相互作用以及 CD40L 的表达被认为与骨髓瘤细胞的发展密切相关。本研究探讨了 EBV 感染对肝移植后骨髓瘤细胞表型和生物学行为的影响及其机制。采用流式细胞术检测 10 例新鲜分离的多发性骨髓瘤细胞中 CD40 与 CD40L 的共表达。在样本 5、8、9 和 10 中检测到 CD40 和 CD40L 的共表达，尤其是样本 5。Western blot 分析检测到感染 EBV 的多发性骨髓瘤细胞系 RPMI 8226 中 EBV 潜伏膜蛋白 1 和 EBV 核抗原 2 的抗原表达。抗原表达表明 EBV 可在体外感染多发性骨髓瘤病毒细胞。逆转录-聚合酶链反应显示感染的 RPMI 8226 细胞中 CD40L 的表达上调，这可能与感染细胞的抗凋亡活性有关。共聚焦显微镜显示，CD40、CD40L 和潜伏膜蛋白 1 的分子对在感染细胞的表面上共定位。感染 EBV 后，RPMI 8226 细胞上调 CXC 趋化因子受体 4。趋化因子基质细胞衍生因子-1α 的存在可改善感染细胞的迁移能力。抗凋亡和迁移是恶性细胞的重要生物学特征。我们的结果表明 EBV 参与多发性骨髓瘤的起源和发展。当 EBV 感染生发中心的 B 细胞时，多发性骨髓瘤的风险增加，这可能导致 B 细胞的抗凋亡作用以及从生发中心向外周血迁移的能力提高。
