爱普斯坦-巴尔病毒（EBV）通常以潜伏感染的形式存在于免疫能力正常的宿主中，但免疫抑制者有发生EBV复活的风险，从而导致B淋巴细胞的无控制增殖。本研究通过使用环孢霉素A（CsA）在树鼩模型中模拟了免疫抑制微环境。结果显示，在体外，EBV共培养的外周血单个核细胞（PBMCs）在CsA处理下迅速增殖。然而，在体内，EBV的易感性取决于CsA的给药时机。经过25mg/kg/日CsA（EBV > CsA组）治疗后，休眠感染了EBV的树鼩发生EBV复活，而如果在注射EBV前连续五周给予CsA（CsA > EBV组），树鼩将不再易感染。对这两组进行的RNA-seq分析揭示了免疫抑制与EBV感染之间的进一步联系。KEGG通路富集分析显示EBV > CsA组中与病毒感染有关的通路富集显著，而CsA > EBV组中肿瘤相关通路富集显著。为了鉴定核心基因，构建了一个蛋白质-蛋白质相互作用网络并使用Cytoscape进行验证。总结起来，树鼩EBV感染模型表现出某些与人类EBV感染相类似的特征，是探索EBV感染的潜在机制的宝贵平台。 版权所有 © 2023. Elsevier Masson SAS 发布。

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.Copyright © 2023. Published by Elsevier Masson SAS.