人补体调节蛋白CD59在水痘-带状疱疹病毒免疫逃逸中的作用研究

水痘-带状疱疹病毒（VZV）是引发水痘与带状疱疹的病原体，目前已发现VZV多种免疫逃逸机制，但仍没有关于VZV逃逸补体的研究报导。本课题组在前期工作中首次发现VZV病毒颗粒包装有人补体调节蛋白CD59，以及在SCID-hu人鼠嵌合模型中VZV感染可显著上调人T细胞和神经细胞CD59表达水平。CD59能够抑制补体激活的终末阶段并降低补体杀伤作用，因此以上两个现象提示VZV可能存在依靠CD59逃逸补体攻击的“自我保护”机制。本项目拟通过系统性研究VZV病毒颗粒、VZV感染的人T细胞与神经细胞激活补体系统的特征表现，分析CD59对其抵抗补体攻击的影响，验证“VZV劫持宿主CD59逃逸补体”的科学假设，并评估CD59成为抗VZV感染药物靶标的可行性与潜力，以期为VZV补体逃逸机制的进一步研究奠定理论基础，为“消除VZV逃避补体攻击机制，提高补体杀伤VZV效率” 的抗VZV感染治疗策略提供科学依据。

Varicella-zoster virus (VZV) is the causative agent of both chickenpox and shingles. To date, multiple immune evasion mechanisms of VZV have been identified, however, few studies have addressed the complement evasion strategies used by this virus. In previous work our group has first found that VZV incorporates host complement regulator CD59 into the viral envelope, and VZV infection significantly upregulates expression of CD59 in human T cells and neural cells in SCID-hu mice. CD59 can inhibit the final stage of complement activation and suppress complement-mediated lysis. Therefore, the above observations suggest that VZV is likely to use a CD59-dependent ‘self-protection’ mechanism to escape from host complement attack. In this project, we will investigate systematically the serum complement activation by VZV virus particles and VZV-infected human T cells and neural cells, and we will evaluate the effect of CD59 on their sensitivity to complement attack as well. We expect the results will confirm our hypothesis that VZV hijacks host CD59 for complement evasion, and determine the feasibility and potential of CD59 as a drug target for anti-VZV therapy, which will not only help further investigation into mechanisms of VZV complement evasion, but also provide evidence that targeting VZV complement-evasion can serve as an antiviral strategy against VZV infection.