Rodríguez-Frade José M, Guedán Anabel, Lucas Pilar, Martínez-Muñoz Laura, Villares Ricardo, Criado Gabriel, Balomenos Dimitri, Reyburn Hugh T, Mellado Mario
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.
Inflammatory and Autoimmune Diseases Group, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Front Immunol. 2017 Apr 21;8:460. doi: 10.3389/fimmu.2017.00460. eCollection 2017.
During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fas-mediated apoptosis is central to the maintenance of T cell homeostasis and prevention of autoimmune processes. We prepared LVP that express murine FasL on their surface. Our data indicate that mFasL-bearing LVP induce caspase 3 and 9 processing, cytochrome C release, and significantly more cell death than control LVP . This cytotoxicity is blocked by the caspase inhibitor Z-VAD. Analysis of the application of these reagents for the treatment of inflammatory arthritis suggests that FasL-expressing LVP could be useful for therapy in autoimmune diseases such as rheumatoid arthritis, where there is an excess of Fas-expressing activated T cells in the joint. LVP could be a vehicle not only for mFasL but also for other membrane-bound proteins that maintain their native conformation and might mediate biological activities.
在出芽过程中，慢病毒颗粒（LVP）会将细胞膜蛋白整合到病毒包膜中。我们探索了利用这一过程来生成表达具有治疗意义的膜蛋白的LVP的可能性，并研究了这些工具治疗不同病理状况的潜力。Fas介导的细胞凋亡对于维持T细胞稳态和预防自身免疫过程至关重要。我们制备了在其表面表达小鼠FasL的LVP。我们的数据表明，携带mFasL的LVP诱导半胱天冬酶3和9的加工、细胞色素C的释放，并且比对照LVP显著诱导更多的细胞死亡。这种细胞毒性被半胱天冬酶抑制剂Z-VAD阻断。对这些试剂用于治疗炎性关节炎的分析表明，表示FasL的LVP可能对治疗自身免疫性疾病（如类风湿性关节炎）有用，在类风湿性关节炎中，关节中存在过量表达Fas的活化T细胞。LVP不仅可以作为mFasL的载体，还可以作为其他保持其天然构象并可能介导生物活性的膜结合蛋白的载体。
