Holder Kayla A, Grant Michael D
Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Front Cell Infect Microbiol. 2020 May 5;10:175. doi: 10.3389/fcimb.2020.00175. eCollection 2020.
During chronic human immunodeficiency virus type 1 (HIV-1) infection, upregulation of inhibitory molecules contributes to effector cell dysfunction and exhaustion. This, in combination with the ability of HIV-1 to reside dormant in cellular reservoirs and escape immune recognition, makes the pathway to HIV-1 cure particularly challenging. An idealized strategy to achieve HIV-1 cure proposes combined viral and immune activation by "shock"ing HIV-1 out of latency and into an immunologically visible state to be recognized and "kill"ed by immune effector cells. Here we outline the potential for blockade of the inhibitory immune checkpoint T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) to overcome natural killer (NK) cell and T cell inhibition associated with HIV-1 infection and invigorate antiviral effector cell responses against HIV-1 reactivated from the latent cellular reservoir.
在慢性1型人类免疫缺陷病毒（HIV-1）感染期间，抑制性分子的上调会导致效应细胞功能障碍和耗竭。这与HIV-1潜伏在细胞储存库并逃避免疫识别的能力相结合，使得实现HIV-1治愈的途径极具挑战性。一种理想的实现HIV-1治愈的策略是通过“冲击”使HIV-1从潜伏状态转为免疫可见状态，从而实现病毒和免疫的联合激活，以便被免疫效应细胞识别并“清除”。在此，我们概述了阻断具有免疫球蛋白和免疫受体酪氨酸抑制基序结构域的抑制性免疫检查点T细胞免疫受体（TIGIT）的潜力，以克服与HIV-1感染相关的自然杀伤（NK）细胞和T细胞抑制，并增强针对从潜伏细胞储存库重新激活的HIV-1的抗病毒效应细胞反应。
