Per-1短异构体抑制静息CD4+ T细胞中HIV-1的从头转录。
The Per-1 Short Isoform Inhibits de novo HIV-1 Transcription in Resting CD4+ T-cells.
作者信息
Zhao Li, Liu Mei, Ouyang Jiayue, Zhu Zheming, Geng Wenqing, Dong Jinxiu, Xiong Ying, Wang Shumei, Zhang Xiaowei, Qiao Ying, Ding Haibo, Sun Hong, Liang Guoxin, Shang Hong, Han Xiaoxu
机构信息
Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, Shenyang, China.
The Core Laboratory for Public Health Science and Practice, The First Affiliated Hospital, China Medical University, Shenyang, China.
出版信息
Curr HIV Res. 2018;16(6):384-395. doi: 10.2174/1570162X17666190218145048.
BACKGROUND
Understanding of the restriction of HIV-1 transcription in resting CD4+ Tcells is critical to find a cure for AIDS. Although many negative factors causing HIV-1 transcription blockage in resting CD4+ T-cells have been found, there are still unknown mechanisms to explore.
OBJECTIVE
To explore the mechanism for the suppression of de novo HIV-1 transcription in resting CD4+ T-cells.
METHODS
In this study, a short isoform of Per-1 expression plasmid was transfected into 293T cells with or without Tat's presence to identify Per-1 as a negative regulator for HIV-1 transcription. Silencing of Per-1 was conducted in resting CD4+ T-cells or monocyte-derived macrophages (MDMs) to evaluate the antiviral activity of Per-1. Additionally, we analyzed the correlation between Per-1 expression and viral loads in vivo, and silenced Per-1 by siRNA technology to investigate the potential anti-HIV-1 roles of Per-1 in vivo in untreated HIV-1-infected individuals.
RESULTS
We found that short isoform Per-1 can restrict HIV-1 replication and Tat ameliorates this inhibitory effect. Silencing of Per-1 could upregulate HIV-1 transcription both in resting CD4+ Tcells and MDMs. Moreover, Per-1 expression is inversely correlated with viral loads in Rapid progressors (RPs) in vivo.
CONCLUSION
These data together suggest that Per-1 is a novel negative regulator of HIV-1 transcription. This restrictive activity of Per-1 to HIV-1 replication may contribute to HIV-1 latency in resting CD4+ T-cells.
背景
了解HIV-1转录在静息CD4+ T细胞中的限制对于找到治愈艾滋病的方法至关重要。尽管已经发现了许多导致静息CD4+ T细胞中HIV-1转录受阻的负面因素，但仍有未知机制有待探索。
目的
探讨静息CD4+ T细胞中HIV-1转录起始抑制的机制。
方法
在本研究中，将Per-1表达质粒的短异构体转染至有或无Tat存在的293T细胞中，以确定Per-1为HIV-1转录的负调节因子。在静息CD4+ T细胞或单核细胞衍生的巨噬细胞（MDM）中沉默Per-1，以评估Per-1的抗病毒活性。此外，我们分析了体内Per-1表达与病毒载量之间的相关性，并通过siRNA技术沉默Per-1，以研究Per-1在未经治疗的HIV-1感染个体体内的潜在抗HIV-1作用。
结果
我们发现短异构体Per-1可以限制HIV-1复制，而Tat可改善这种抑制作用。沉默Per-1可上调静息CD4+ T细胞和MDM中的HIV-1转录。此外，体内快速进展者（RP）中Per-1表达与病毒载量呈负相关。
结论
这些数据共同表明Per-1是HIV-1转录的新型负调节因子。Per-1对HIV-1复制的这种限制活性可能导致HIV-1在静息CD4+ T细胞中的潜伏。
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