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。
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