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研究揭示感染的T细胞库中的HIV沉默和细胞生存特征
2023-01-07 15:23

美国国立卫生研究院Eli A. Boritz等研究人员合作揭示感染的T细胞库中的HIV沉默和细胞生存特征。2023年1月4日,国际知名学术期刊《自然》在线发表了这一成果。

据研究人员介绍,在抗逆转录病毒疗法下含有艾滋病毒的罕见CD4 T细胞是治愈艾滋病毒的一个重要障碍,但在自然状态下分离和描述这些细胞的不可行性导致不确定它们是否具有HIV治愈指导疗法可能利用的独特属性。

研究人员使用一种微流控技术来解决这一挑战,该技术仅根据HIV DNA的检测来分离HIV感染细胞的转录组。接受抗逆转录病毒治疗的人血液中的HIV-DNA+记忆CD4 T细胞显示出对六种转录组途径的抑制,包括死亡受体信号、坏死信号和抗增殖的Gα12/13信号。此外,通过网络共表达分析确定的两组基因与HIV-DNA+细胞显著相关。这些基因(n=145)仅占测量的转录组的0.81%,包括在HIV-DNA+细胞中较高的HIV转录的负调控因子,在HIV-DNA+细胞中较低的HIV转录的正调控因子,以及参与RNA处理、mRNA翻译的负调控和细胞状态和命运调控的其他基因。这些发现显示,在抗逆转录病毒治疗下,HIV感染的记忆性CD4 T细胞是一个独特的群体,其宿主基因表达模式有利于HIV沉默、细胞生存和细胞增殖,这对HIV治愈策略的发展具有重要意义。
 
附:英文原文

Title: HIV silencing and cell survival signatures in infected T cell reservoirs

Author: Clark, Iain C., Mudvari, Prakriti, Thaploo, Shravan, Smith, Samuel, Abu-Laban, Mohammad, Hamouda, Mehdi, Theberge, Marc, Shah, Sakshi, Ko, Sung Hee, Prez, Liliana, Bunis, Daniel G., Lee, James S., Kilam, Divya, Zakaria, Saami, Choi, Sally, Darko, Samuel, Henry, Amy R., Wheeler, Michael A., Hoh, Rebecca, Butrus, Salwan, Deeks, Steven G., Quintana, Francisco J., Douek, Daniel C., Abate, Adam R., Boritz, Eli A.

Issue&Volume: 2023-01-04

Abstract: Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure1,2,3, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA+ memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling. Moreover, two groups of genes identified by network co-expression analysis were significantly associated with HIV-DNA+ cells. These genes (n=145) accounted for just 0.81% of the measured transcriptome and included negative regulators of HIV transcription that were higher in HIV-DNA+ cells, positive regulators of HIV transcription that were lower in HIV-DNA+ cells, and other genes involved in RNA processing, negative regulation of mRNA translation, and regulation of cell state and fate. These findings reveal that HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population with host gene expression patterns that favour HIV silencing, cell survival and cell proliferation, with important implications for the development of HIV cure strategies.

DOI: 10.1038/s41586-022-05556-6

Source: https://www.nature.com/articles/s41586-022-05556-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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