Immunological effector mechanisms in HIV-1 elite controllers.
Immunological effector mechanisms in HIV-1 elite controllers.
复制标题
HIV-1精英控制者的免疫效应机制。
DOI：
10.1097/coh.0000000000000693
复制
发表时间：
2021-09-01
影响因子：
4.1
通讯作者：
Yu XG
中科院分区：
文献类型：
--
作者：
Hartana CA;Yu XG
HIV-1精英控制者包括少数HIV-1感染者，他们在没有抗逆转录病毒治疗的情况下，可以自发地将血浆病毒载量控制在检测限以下。抗病毒免疫反应可能有助于这种令人印象深刻的HIV-1疾病的结果。在这篇综述中，我们讨论了最近的新发现，抗病毒的先天性和适应性免疫反应的精英控制器。精英控制者维持一个受感染细胞池，其中完整的HIV-1前病毒更频繁地整合在宿主基因组的非编码区，可能赋予深度潜伏状态。这种非典型的病毒储库配置最好的解释是有效的抗病毒免疫反应，可以成功地消除病毒感染的细胞，其中前病毒整合在允许的染色质。然而，确定这种免疫选择压力的具体类型和性质是一个艰巨的挑战。最近的研究继续支持HIV-1特异性CD 8 + T细胞作为HIV-1精英免疫控制的主要驱动力的作用，然而，越来越多的证据表明，它们的作用是通过与先天免疫细胞亚群的微调相互作用来补充的。因此，不同免疫效应机制的组合可能会塑造精英控制者的抗病毒免疫。了解负责自然，无毒HIV-1控制的复杂免疫机制是寻找和开发治疗HIV-1感染的干预措施的首要途径。未来的单细胞检测旨在揭示精英控制者抗病毒免疫反应的完整遗传、表观遗传、转录和功能复杂性，这可能使我们能够更详细地定义抗病毒免疫保护的相关性。
HIV-1 elite controllers encompass small populations of people infected with HIV-1 who can spontaneously control plasma viral loads below the limit of detection, in the absence of antiretroviral treatment. Antiviral immune responses are likely to contribute to such an impressive HIV-1 disease outcome. In this review, we discuss recent novel findings regarding antiviral innate and adaptive immune responses in elite controllers. Elite controllers maintain a pool of infected cells in which intact HIV-1 proviruses are more frequently integrated in non-coding regions of the host genome, likely conferring a state of deep latency. This atypical viral reservoir configuration is best explained by potent antiviral immune responses that can successfully eliminate virally infected cells in which proviruses are integrated in permissive chromatin. However, identifying the specific type and nature of this immune selection pressure represents a formidable challenge. Recent studies continue to support the role of HIV-1-specific CD8+ T cells as the main driver of elite immune control of HIV-1, however, increasing evidence suggests that their role is complemented by a fine-tuned interplay with innate immune cell subsets. Therefore, the combination of different immune effector mechanisms may shape antiviral immunity in elite controllers. Understanding the complex immune mechanisms responsible for natural, drug-free HIV-1 control represents a premier avenue to find and develop interventions for a cure of HIV-1 infection. Future single-cell assays designed to uncover the full genetic, epigenetic, transcriptional and functional complexity of antiviral immune responses in elite controllers may allow us to define correlates of antiviral immune protection in greater detail.