Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.
Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.
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DOI：
10.1371/journal.ppat.1005201
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发表时间：
2015-10
期刊：
影响因子：
6.7
通讯作者：
Margolis DM
中科院分区：
文献类型：
--
作者：
Soriano-Sarabia N;Archin NM;Bateson R;Dahl NP;Crooks AM;Kuruc JD;Garrido C;Margolis DM
根除艾滋病毒感染将需要识别潜伏感染的所有细胞储存库。尽管CD4受体在Vδ2 T细胞上低表达或缺乏表达，但这些细胞的感染先前已有报道。我们发现CD4受体的上调可能使原代Vδ2细胞成为体外HIV感染的靶标，我们提出HIV诱导的免疫激活可能允许体内γδ T细胞感染。我们通过对18例长期接受抗逆转录病毒治疗的病毒血症患者的Vδ2细胞内的DNA测量和生长测定来评估潜伏性HIV感染的存在。在14例患者中，我们从高度纯化的Vδ2细胞中恢复了潜伏但具有复制能力的HIV，这表明外周Vδ2 T细胞是一个以前未被识别的库，其中潜伏的HIV感染出乎意料地频繁。抗逆转录病毒治疗（ART）已导致全球艾滋病毒相关发病率和死亡率下降。虽然成功的抗逆转录病毒治疗可以恢复健康，但它并不能治愈感染，因为潜伏的HIV-1仍然整合在不同的细胞群中，不受抗逆转录病毒治疗的影响。迄今为止，静止记忆CD4+ T细胞是最具特征的细胞储存库。然而，根除HIV-1感染需要描述所有潜伏的细胞储存库，其中包含具有复制能力的HIV-1。我们描述了在γδ T淋巴细胞中发现的意想不到的细胞库。这种新的储存库必须考虑的策略，以清除潜伏的艾滋病毒是开发和测试。
Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection in vitro and we propose that HIV-induced immune activation may allow infection of γδ T cells in vivo. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent. Antiretroviral therapy (ART) has led to a decreased HIV-related morbidity and mortality across the world. While successful ART restores health, it does not cure infection as latent HIV-1 remains integrated within different cell populations, unaffected by ART. To date resting memory CD4+ T cells are the best-characterized cellular reservoir. However, eradication of HIV-1 infection requires the description of all latent cellular reservoirs harboring replication-competent HIV-1. We describe the discovery of an unexpected cellular reservoir within γδ T lymphocytes. This novel reservoir must be considered as strategies to clear latent HIV are developed and tested.