通过NRF1介导的线粒体生物生成对抗了先天的抗病毒免疫力
Tian Zhao1, Jiaojiao Zhang1, Hong Lei1
1State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China.
The EMBO journal
|July 6, 2023
概括
病毒劫持线粒体生物发生,以抑制免疫力. 抑制核呼吸因子-1 (NRF1) 通过防止线粒体损伤和DNA释放来增强抗病毒防御,揭示了一个新的免疫反循环.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 线粒体生物发生对于细胞平衡至关重要.
- 病毒可以操纵宿主细胞的复制过程.
- 天生的免疫力提供了对病毒感染的第一道防线.
研究的目的:
- 为了研究线粒体生物发生在病毒感染中的作用.
- 为了确定病毒诱导的线粒体生物发生的关键调节者.
- 阐明病毒对抗天生的抗病毒免疫力的机制.
主要方法:
- 在小鼠模型中利用RNA (VSV) 和DNA (HSV-1) 病毒.
- 评估了核呼吸因子-1 (NRF1) 缺乏对病毒载量和免疫力的影响.
- 研究了由TBK1激酶对NRF1的酸化.
- 采用一个敲进 (KI) 策略来模仿TBK1-NRF1信号.
主要成果:
- NRF1对于病毒诱导的线粒体生物发生是必不可少的.
- 缺乏NRF1可以增强先天免疫力,降低病毒载量,降低发病率.
- 抑制NRF1介导生物发生会增加线粒体损伤,mtDNA释放和mtROS产生.
- TBK1酸化NRF1,使NRF1-TFAM轴不活化,并促进病毒复制.
- 打断TBK1-NRF1相互作用减弱了抗病毒反应.
结论:
- 病毒利用NRF1介导的线粒体生物发生来抑制先天的抗病毒免疫力.
- 在病毒感染期间,NRF1充当先天免疫的负反调节器.
- 针对TBK1-NRF1相互作用提供了增强抗病毒防御的潜在策略.
相关概念视频
NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K
Immune Response Against Viral Pathogens
829
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...
829
RNA Interference
26.1K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.1K
Viruses with RNA Genomes
58
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...
58
Mechanisms of Retrovirus-induced Cancers
5.1K
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...
5.1K
Electron Transport Chain: Complex I and II
14.6K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
14.6K


