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Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

机译:爱泼斯坦-巴尔病毒感染对肝移植后多发性骨髓瘤发展的影响

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摘要

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.
机译:肝移植后患者细胞免疫功能的降低很容易导致多种类型的病毒感染,例如爱泼斯坦-巴尔病毒。爱泼斯坦-巴尔病毒是一种Γ疱疹病毒,与许多恶性疾病有关,尤其是上皮和淋巴瘤。分化簇40与分化簇40配体的异常相互作用以及分化簇40配体的表达被认为与骨髓瘤细胞的发育密切相关。本研究探讨了爱泼斯坦-巴尔病毒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。流式细胞术用于检测10个新鲜分离的多发性骨髓瘤细胞样品中分化40簇和分化40簇配体的共表达。在样品编号5、8、9和10中,特别是在样品编号5中共表达了分化40簇和分化40簇。感染了爱泼斯坦-巴尔病毒的多发性骨髓瘤细胞系RPMI 8226中的蛋白1和爱泼斯坦-巴尔病毒核抗原2。抗原表达表明爱泼斯坦-巴尔病毒可在体外感染多种骨髓瘤病毒细胞。逆转录-聚合酶链反应显示感染的RPMI 8226细胞上分化40配体簇的表达上调,这可能与感染细胞的抗凋亡活性有关。共聚焦显微镜检查显示,成对的分化簇40,分化簇40配体和潜伏膜蛋白1分子共定位在感染细胞的表面。爱泼斯坦-巴尔病毒感染后,RPMI 8226细胞上的CXC趋化因子受体4上调。在趋化因子基质细胞衍生因子-1α的存在下,感染细胞的迁移能力得到改善。抗凋亡和迁移是已知的恶性细胞的重要生物学特性。我们的结果表明爱泼斯坦-巴尔病毒参与多发性骨髓瘤的起源和发展。当爱泼斯坦-巴尔病毒感染生发中心的B细胞时,多发性骨髓瘤的风险会增加,这可能会导致B细胞的抗凋亡作用,并提高从生发中心迁移至外周血的能力。

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