Tetherin是人体细胞天然存在的抗病毒因子，其抗病毒机理是通过穿膜区和锚定区将新生病毒颗粒束缚在被感染细胞表面，阻止病毒释放，其抗病毒作用可被HIV-1 Vpu拮抗，机制目前尚有争论。本课题基于已有理论及前期研究基础，对此问题提出一种新的解释。即Vpu通过与TASK通道蛋白相互作用引发细胞表面电位变化，触发电压依赖性钙通道（VDCC），导致钙离子内流，激活磷脂酶C（PLC）切除Tetherin的锚定区GPI修饰，使其抗病毒活性丧失，同时释放三磷酸肌醇（IP3）信号，进一步提升胞浆钙离子浓度，产生级联放大作用。本课题将通过钙离子调控剂干预、同位素示踪和RNA干扰等实验手段证实GPI修饰对Tetherin功能的影响及PLC和钙离子对其功能的阻断作用，揭示一条通过钙离子介导的Vpu拮抗Tetherin作用途径，从一个全新角度阐明Vpu增强病毒释放的分子机制，为抗艾滋病治疗提供新思路和新靶点。

Tetherin is a natural host antiviral factor,it restricts virus by tethering viral particles to the infected cell surface through its transmembrane domain and Glycophosphatidylinositol(GPI) anchor, and prevents virus release. HIV-1 Viral Protein U(Vpu)efficiently antagonizes this antiviral activity, but the mechanism is still controversial. This proposal is based on existing theory and preliminary research data, and presents a new interpretation for conteraction mechanism between Vpu and tetherin. Vpu interacts with TASK channel protein, causes changes of cell surface potential and triggers voltage-dependent calcium channel (VDCC), leading to calcium influx, which activates phospholipase C (PLC) to remove GPI modification of tetherin anchor and eliminate its antiviral activity. Simultaneously, inositol triphosphate (IP3) signal would be released, resulting in further enhanced intracellular calcium concentration and a cascade effect,which would enhance the effect of PLC's modification. This proposal would address through intervention of calcium regulating agent, isotope tracing and RNA interference experiments to confirm the contribution of GPI modification and the blocking effect of PLC and calcium ions to the tetherin function, and reveal a Vpu-induced calcium-mediated tetherin antagonism pathway. It would explain the molecular mechanism of Vpu enhanced virus release from a new angle, and provide new ideas and novel targets for anti-Acquired immune deficiency syndrome (AIDS ) treatment.