Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in activated PBMC by a mechanism dependent on gp41 function.
Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in activated PBMC by a mechanism dependent on gp41 function.
复制标题
猫免疫缺陷病毒包膜糖蛋白通过依赖 gp41 功能的机制介导激活的 PBMC 细胞凋亡。
DOI：
10.1016/j.virol.2004.10.007
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发表时间：
2004
期刊：
影响因子：
3.7
通讯作者：
Tompkins,WayneA
中科院分区：
文献类型：
--
作者：
Garg,Himanshu;Joshi,Anjali;Tompkins,WayneA
猫免疫缺陷病毒（FIV）是一种慢病毒，导致猫免疫缺陷，这与人类HIV-1诱导的免疫缺陷相似。已经确定HIV包膜（Env）糖蛋白通过需要CXCR 4结合的机制介导T细胞损失。FIV的Env糖蛋白类似于HIV，需要CXCR 4结合以用于病毒进入，以及诱导膜融合，从而导致合胞体形成。然而，FIV Env在T细胞损失中的作用以及控制该过程的分子机制尚未阐明。我们在体外模型中研究了Env糖蛋白在FIV介导的T细胞凋亡中的作用。我们的研究表明，膜表达的FIV Env通过需要CXCR 4结合的机制诱导活化的猫外周血单核细胞（PBMC）的凋亡，因为该过程被CXCR 4拮抗剂AMD 3100以剂量依赖性方式抑制。有趣的是，关于CD 134（最近鉴定的FIV的主要受体）的作用的研究表明，与CD 134的结合对于PBMC中的细胞凋亡的诱导可能并不重要。然而，通过FIV gp 41特异性融合抑制剂抑制CXCR 4结合后Env介导的融合也抑制细胞凋亡。在相似的条件下，融合缺陷型gp 41突变体不能诱导活化的PBMC凋亡。我们的研究结果是第一份报告，表明FIV Env通过依赖于gp 41功能的过程介导旁观者细胞凋亡的潜力。
Feline Immunodeficiency Virus (FIV) is a lentivirus that causes immunodeficiency in cats, which parallels HIV-1-induced immunodeficiency in humans. It has been established that HIV envelope (Env) glycoprotein mediates T cell loss via a mechanism that requires CXCR4 binding. The Env glycoprotein of FIV, similar to HIV, requires CXCR4 binding for viral entry, as well as inducing membrane fusion leading to syncytia formation. However, the role of FIV Env in T cell loss and the molecular mechanisms governing this process have not been elucidated. We studied the role of Env glycoprotein in FIV-mediated T cell apoptosis in an in vitro model. Our studies demonstrate that membrane-expressed FIV Env induces apoptosis in activated feline peripheral blood mononuclear cells (PBMC) by a mechanism that requires CXCR4 binding, as the process was inhibited by CXCR4 antagonist AMD3100 in a dose-dependent manner. Interestingly, studies regarding the role of CD134, the recently identified primary receptor of FIV, suggest that binding to CD134 may not be important for induction of apoptosis in PBMC. However, inhibiting Env-mediated fusion post CXCR4 binding by FIV gp41-specific fusion inhibitor also inhibited apoptosis. Under similar conditions, a fusion-defective gp41 mutant was unable to induce apoptosis in activated PBMC. Our findings are the first report suggesting the potential of FIV Env to mediate apoptosis in bystander cells by a process that is dependent on gp41 function.