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.

中文翻译：

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TRAIL：HIV 免疫病理学中的 TRAILshort 轴。

HIV 感染和未感染的 CD4 T 细胞加速丢失是 HIV 感染的标志，会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 的障碍涉及病毒作为潜伏病毒库保持静止状态并操纵宿主防御以促进病毒存活和受感染库的持久性的能力。几种机制导致 CD4 T 细胞耗竭，最近的研究证明了肿瘤坏死因子相关的凋亡诱导配体 (TRAIL) 在此过程中的作用。TRAIL 及其受体的表达响应 HIV 感染而上调。TRAIL 与其受体相互作用以激活细胞凋亡途径。我们最近证明了全长 TRAIL 的新型剪接变体 TRAILshort 的存在，在 HIV 感染者的血清中。独特的羧基末端允许 TRAILshort 与死亡受体结合而不诱导细胞凋亡，并阻止 TRAIL 与其受体结合，从而赋予对 TRAIL 介导的死亡的抵抗力。在这篇综述中，我们描述了 TRAIL：TRAILshort 受体轴如何在 HIV 感染的情况下调节不同类型免疫细胞的凋亡。我们还讨论了 TRAIL 和 TRAILshort 如何促进参与宿主防御 HIV 的免疫细胞的激活，以及 HIV 已经进化为操纵 TRAIL 使其存活的机制。我们描述了 TRAIL：TRAIL 短受体轴如何在 HIV 感染的情况下调节不同类型免疫细胞的凋亡。我们还讨论了 TRAIL 和 TRAILshort 如何促进参与宿主防御 HIV 的免疫细胞的激活，以及 HIV 已经进化为操纵 TRAIL 使其存活的机制。我们描述了 TRAIL：TRAIL 短受体轴如何在 HIV 感染的情况下调节不同类型免疫细胞的凋亡。我们还讨论了 TRAIL 和 TRAILshort 如何促进参与宿主防御 HIV 的免疫细胞的激活，以及 HIV 已经进化为操纵 TRAIL 使其存活的机制。