CD161+ CD4+ T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
CD161+ CD4+ T Cells Harbor Clonally Expanded Replication-Competent HIV-1 in Antiretroviral Therapy-Suppressed Individuals
复制标题
CD161 CD4 T 细胞在抗逆转录病毒治疗抑制的个体中携带克隆扩增的具有复制能力的 HIV-1
DOI：
10.1128/mbio.02121-19
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发表时间：
2019-09-01
期刊：
影响因子：
6.4
通讯作者：
Deng, Kai
中科院分区：
文献类型：
--
作者：
Li, Xiaomin;Liu, Zhaoli;Deng, Kai
尽管有有效的抗逆转录病毒疗法，但极其稳定的HIV-1潜伏库的存在是根除的主要障碍。最近的研究表明，在没有病毒再激活的情况下，潜伏感染细胞的克隆扩增是维持水库长期稳定的重要现象，但其潜在机制仍不清楚。在这里，我们报告了一个亚群的CD 4（+）T细胞，其特征是CD 161表达的表面上，是高度允许的HIV-1感染。这些细胞具有比它们的CD 161阴性对应物显著更高的存活和增殖能力。更重要的是，我们发现这些细胞以更高的频率携带HIV-1 DNA和具有复制能力的潜伏病毒。通过对ART抑制个体进行大规模单基因组前病毒测序，我们证实了CD 161（+）CD 4（+）T细胞含有明显更多相同的前病毒序列，表明这些细胞中病毒基因组的克隆扩增。综上所述，我们的研究确定了受感染的CD 161（+）CD 4（+）T细胞是驱动HIV-1潜伏库克隆扩张的关键力量，为HIV-1潜伏期的长期稳定性提供了一种新的机制。重要性潜伏库仍然是治愈HIV-1感染的主要障碍。潜伏感染细胞的克隆扩增增加了另一层，维持了水库的长期稳定性，但其机制尚不清楚。在这里，我们报道了CD 161（+）CD 4（+）T细胞作为HIV-1潜伏库的一个重要部分，并含有大量的克隆扩增的前病毒。在我们的研究中，我们描述了一种可行的策略，可以通过平衡潜伏感染细胞的再增殖和传播来在一定程度上减少潜伏水库的大小。
The presence of an extremely stable latent reservoir of HIV-1 is the major obstacle to eradication, despite effective antiretroviral therapy (ART). Recent studies have shown that clonal expansion of latently infected cells without viral reactivation is an important phenomenon that maintains the long-term stability of the reservoir, yet its underlying mechanism remains unclear. Here we report that a subset of CD4(+) T cells, characterized by CD161 expression on the surface, is highly permissive for HIV-1 infection. These cells possess a significantly higher survival and proliferative capacity than their CD161-negative counterparts. More importantly, we found that these cells harbor HIV-1 DNA and replication-competent latent viruses at a significantly higher frequency. By using massive single-genome proviral sequencing from ART-suppressed individuals, we confirm that CD161(+) CD4(+) T cells contain remarkably more identical proviral sequences, indicating clonal expansion of the viral genome in these cells. Taking the results together, our study identifies infected CD161(+) CD4(+) T cells to be a critical force driving the clonal expansion of the HIV-1 latent reservoir, providing a novel mechanism for the long-term stability of HIV-1 latency.IMPORTANCE The latent reservoir continues to be the major obstacle to curing HIV-1 infection. The clonal expansion of latently infected cells adds another layer maintaining the long-term stability of the reservoir, but its mechanism remains unclear. Here, we report that CD161(+) CD4(+) T cells serve as an important compartment of the HIV-1 latent reservoir and contain a significant amount of clonally expanded proviruses. In our study, we describe a feasible strategy that may reduce the size of the latent reservoir to a certain extent by counterbalancing the repopulation and dissemination of latently infected cells.