Shi Nan, Chen Honglin, Lai Yongjing, Luo Zhenqiu, Huang Zongjian, He Guangyao, Yi Xiang, Xia Wei, Tang Anzhou
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530000, China; Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530000, China; Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.
Microbes Infect. 2023 Nov-Dec;25(8):105212. doi: 10.1016/j.micinf.2023.105212. Epub 2023 Aug 24.
Epstein-Barr virus (EBV) usually exists as a latent infection in immunocompetent hosts but immunosuppressed individuals are at risk for developing EBV reactivation that leads to the uncontrolled proliferation of B lymphocytes. In this study, we have mimicked the immunosuppressed microenvironment in the tree shrew model of EBV infection by using cyclosporine A (CsA). The results showed that EBV-cocultured peripheral blood mononuclear cells (PBMCs) proliferated vigorously in response to CsA treatment in vitro. However, EBV susceptibility in vivo depended on the timing of CsA administration. Reactivation of EBV occurred in the latently EBV-infected tree shrews after treatment with 25 mg/kg/day CsA (EBV > CsA group), whereas tree shrews were no longer susceptible to infection if CsA was administered for five weeks before EBV injection (CsA > EBV group). RNA-seq analysis of both groups identified a further link between immunosuppression and EBV infection. KEGG pathway enrichment analysis revealed a significant enrichment of viral infection-related pathways in the EBV > CsA group, whereas tumor-related pathways were significantly enriched in the CsA > EBV group. A protein-protein interaction network was constructed using Cytoscape for the purpose of identifying hub genes that were then verified using qRT-PCR. In conclusion, the tree shrew model of EBV infection exhibits certain features of EBV infection in humans and serves as a valuable platform for exploring the underlying mechanisms of EBV infection.
爱泼斯坦-巴尔病毒（EBV）在免疫功能正常的宿主中通常以潜伏感染的形式存在，但免疫抑制个体有发生EBV再激活的风险，这会导致B淋巴细胞不受控制地增殖。在本研究中，我们通过使用环孢素A（CsA）在树鼩EBV感染模型中模拟了免疫抑制微环境。结果表明，体外经CsA处理后，与EBV共培养的外周血单个核细胞（PBMCs）大量增殖。然而，体内EBV易感性取决于CsA给药时间。用25mg/kg/天的CsA处理后，潜伏感染EBV的树鼩发生了EBV再激活（EBV＞CsA组），而如果在注射EBV前5周给予CsA，树鼩则不再易受感染（CsA＞EBV组）。两组的RNA测序分析确定了免疫抑制与EBV感染之间的进一步联系。KEGG通路富集分析显示，EBV＞CsA组中病毒感染相关通路显著富集，而CsA＞EBV组中肿瘤相关通路显著富集。使用Cytoscape构建了蛋白质-蛋白质相互作用网络，以识别枢纽基因，然后用qRT-PCR进行验证。总之，树鼩EBV感染模型展现了人类EBV感染的某些特征，是探索EBV感染潜在机制的宝贵平台。
