Ragon Institute of MGH, MIT and Harvard, Cambridge.
Infectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Curr Opin HIV AIDS. 2021 Sep 1;16(5):243-248. doi: 10.1097/COH.0000000000000693.
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 into noncoding 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 into 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.
HIV-1 精英控制者是指一小部分感染 HIV-1 的人群，他们在没有抗逆转录病毒治疗的情况下，能够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实现如此令人印象深刻的 HIV-1 疾病结局。在这篇综述中，我们讨论了最近关于精英控制者的抗病毒先天和适应性免疫反应的新发现。
精英控制者维持着一个感染细胞池，其中完整的 HIV-1 前病毒更频繁地整合到宿主基因组的非编码区域，可能导致深度潜伏状态。这种非典型的病毒储存库配置最好通过强大的抗病毒免疫反应来解释，这种反应可以成功消除前病毒整合到允许染色质中的病毒感染细胞。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 CD8+ T 细胞作为精英控制 HIV-1 的主要驱动因素，但越来越多的证据表明，它们的作用与先天免疫细胞亚群的精细相互作用相辅相成。因此，不同免疫效应机制的结合可能会影响精英控制者的抗病毒免疫。
了解负责自然、无药物 HIV-1 控制的复杂免疫机制代表了寻找和开发 HIV-1 感染治愈方法的首要途径。未来旨在揭示精英控制者中抗病毒免疫反应的完整遗传、表观遗传、转录和功能复杂性的单细胞分析，可能使我们能够更详细地定义抗病毒免疫保护的相关性。
