Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.
Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.
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DOI：
10.3389/fimmu.2022.858383
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
尽管抗逆转录病毒疗法（ART）极大地改变了人类免疫缺陷病毒-1 （HIV-1）感染者的生活，但长期治疗与大量合并症有关。因此，治愈HIV-1仍然是全球根除HIV-1/获得性免疫缺陷综合征（AIDS）的最佳选择。然而，制定完全根除艾滋病毒-1的战略一直极具挑战性。因此，通过宿主免疫系统控制HIV-1复制，即功能性治愈，长期以来一直被研究作为HIV-1治愈的替代方法。HIV-1精英控制者（ec）是罕见的个体，他们在没有抗逆转录病毒治疗的情况下自然地保持无法检测到的HIV-1复制水平，他们的免疫库可能是功能性治愈的理想蓝图。虽然不同的人类白细胞抗原（HLA）表达和表达同源配体的CD8+ T细胞反应在ECs中控制HIV-1的作用已被广泛表征，但先天免疫表型的研究显然不足。相比之下，在动物模型中，如hiv -1感染的人源化小鼠和猴免疫缺陷病毒（SIV）感染的非人灵长类动物（NHP），已知病毒毒控制与特定的主要组织相容性复合体（MHC）等位基因和CD8+ T细胞活性有关，但先天免疫反应仍未完全表征。值得注意的是，最近的研究表明，训练先天免疫的存在可能为实现HIV-1治愈提供新的补充方法。在此，我们回顾了已知的ECs先天免疫反应的特征和现有的动物模型，确定了适应性或训练先天免疫细胞反应的知识空白，并推测了在HIV-1非控制者中诱导ec样反应的潜在策略。
Although antiretroviral therapy (ART) has drastically changed the lives of people living with human immunodeficiency virus-1 (HIV-1), long-term treatment has been associated with a vast array of comorbidities. Therefore, a cure for HIV-1 remains the best option to globally eradicate HIV-1/acquired immunodeficiency syndrome (AIDS). However, development of strategies to achieve complete eradication of HIV-1 has been extremely challenging. Thus, the control of HIV-1 replication by the host immune system, namely functional cure, has long been studied as an alternative approach for HIV-1 cure. HIV-1 elite controllers (ECs) are rare individuals who naturally maintain undetectable HIV-1 replication levels in the absence of ART and whose immune repertoire might be a desirable blueprint for a functional cure. While the role(s) played by distinct human leukocyte antigen (HLA) expression and CD8+ T cell responses expressing cognate ligands in controlling HIV-1 has been widely characterized in ECs, the innate immune phenotype has been decidedly understudied. Comparably, in animal models such as HIV-1-infected humanized mice and simian Immunodeficiency Virus (SIV)-infected non-human primates (NHP), viremic control is known to be associated with specific major histocompatibility complex (MHC) alleles and CD8+ T cell activity, but the innate immune response remains incompletely characterized. Notably, recent work demonstrating the existence of trained innate immunity may provide new complementary approaches to achieve an HIV-1 cure. Herein, we review the known characteristics of innate immune responses in ECs and available animal models, identify gaps of knowledge regarding responses by adaptive or trained innate immune cells, and speculate on potential strategies to induce EC-like responses in HIV-1 non-controllers.
HIV 通过 1 型干扰素途径感染和消耗 CD4 1 族 ILC
影响因子：
6.7
作者：
Zhao J;Cheng L;Wang H;Yu H;Tu B;Fu Q;Li G;Wang Q;Sun Y;Zhang X;Liu Z;Chen W;Zhang L;Su L;Zhang Z
通讯作者：
Zhang Z
影响因子：
0.7
作者：
Wambua D;Henderson R;Solomon C;Hunter M;Marx P;Sette A;Mothé BR
通讯作者：
Mothé BR