The TRAIL: TRAILshort Axis in HIV Immunopathology.
The TRAIL: TRAILshort Axis in HIV Immunopathology.
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DOI：
10.1615/critrevimmunol.2019029632
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发表时间：
2018
影响因子：
1.3
通讯作者：
Badley AD
中科院分区：
文献类型：
--
作者：
Aboulnasr F;Paranjape G;Badley AD
HIV感染和未感染的CD4 T细胞的加速损失是HIV感染的标志，导致严重的免疫缺陷，使宿主容易受到机会性感染和恶性肿瘤的影响。根除HIV的障碍包括病毒作为潜伏病毒库保持静止状态的能力，以及操纵宿主防御以利于病毒存活和受感染宿主的持久性。几种机制导致CD4 T细胞耗竭，最近的研究表明肿瘤坏死因子相关凋亡诱导配体（TRAIL）在这一过程中的作用。TRAIL及其受体的表达响应于HIV感染而上调。TRAIL与其受体相互作用以激活凋亡途径。我们最近证实了在HIV感染患者的血清中存在TRAIL短，全长TRAIL的一种新的剪接变体。独特的羧基末端允许TRAIL短结合死亡受体而不诱导凋亡，并阻止TRAIL结合其受体，从而赋予对TRAIL介导的死亡的抗性。在这篇综述中，我们描述了TRAIL：TRAIL短受体轴如何调节不同类型的免疫细胞在HIV感染的背景下凋亡。我们还讨论了TRAIL和TRAIL短如何有助于激活参与宿主防御HIV的免疫细胞，以及HIV进化为操纵TRAIL以使其存活的机制。
Accelerated loss of HIV-infected and uninfected CD4 T cells is a hallmark of HIV infection that leads to severe immunodeficiency, rendering the host susceptible to opportunistic infections and malignancies. Obstacles to eradicating HIV involve the virus’s ability to remain in a quiescent state as latent viral reservoirs and manipulate host defenses to benefit viral survival and persistence of the infected reservoir. Several mechanisms cause CD4 T-cell depletion and recent studies demonstrate the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in this process. Expression of TRAIL and its receptors is upregulated in response to HIV infection. TRAIL interacts with its receptors to activate apoptotic pathways. We recently demonstrated the presence of TRAILshort, a novel splice variant of full-length TRAIL, in the serum of HIV-infected patients. A unique carboxy-terminus allows TRAILshort to bind to death receptors without inducing apoptosis and prevents TRAIL from binding to its receptors, thereby conferring resistance to TRAIL-mediated death. In this review, we describe how the TRAIL: TRAILshort receptor axis modulates apoptosis of different types of immune cells in the context of HIV infection. We also discuss how TRAIL and TRAILshort contribute to the activation of immune cells involved in host defense against HIV and mechanisms that HIV has evolved to manipulate TRAIL for its survival.