艾滋病毒感染将CD4+T细胞重新编程为静止和进入前病毒潜伏期
Leah M Plasek Hegde1,2, Lalith S Gunawardane1, Farshad Niazi1
1Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Nature microbiology
|September 27, 2025
概括
人类免疫缺陷病毒 (HIV) 通过激活p53和克鲁佩尔样因子2 (KLF2) 途径在CD4+ T细胞中建立潜伏储存库. 这一过程使病毒基因沉默,促进了艾滋病毒的持久性,尽管治疗.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 人类免疫缺陷病毒 (HIV) 的持久性是由静止记忆CD4+T细胞中的潜存储库驱动的.
- 了解潜伏水库的形成对于制定消除艾滋病毒的战略至关重要.
研究的目的:
- 阐明 CD4+ T 细胞中潜伏的 HIV 储库形成的分子机制.
- 为了识别由HIV操纵的宿主细胞通路,以使病毒持续存在.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 的人类原发性CD4+T细胞感染HIV.
- 功能研究包括功能损失和功能增益实验和shRNA查.
- 来自HIV阳性捐赠者的T细胞的分析.
主要成果:
- 艾滋病毒感染诱导转录组变化,激活p53通路和KLF2-介导的静止程序.
- 艾滋病毒对KLF2和p53信号进行上调,从而抑制MYC和增殖途径.
- 这导致了前病毒转录沉默,并增强了潜在的储库形成.
结论:
- 艾滋病毒劫持宿主细胞通路 (p53,KLF2) 以诱导静止和转录沉默,促进潜伏储库的形成.
- 这种机制通过创建休眠的病毒储库来确保病毒的持久性.
- 这些发现为治疗策略提供了新的目标,旨在消除潜伏的艾滋病毒储存库.
相关概念视频
Size and Structure of Viral Genomes
691
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
691
Retrovirus Life Cycles
49.3K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
49.3K
Viruses with RNA Genomes
824
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
824
Immune Response Against Viral Pathogens
1.8K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.8K
Mechanisms of Retrovirus-induced Cancers
6.9K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
6.9K
T Cell Activation and Clonal Selection
14.8K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
14.8K


