麻疹病毒通过破坏mTORC1-mTORC2调节回路来逃避细胞检测
Nathan Meade1, Colleen Furey1, Hua Li1
1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cell
|August 7, 2018
概括
脊髓灰质炎病毒使用F17蛋白来破坏细胞mTOR信号,阻断抗病毒反应. 这种保存的病毒策略通过降解病毒DNA的关键传感器cGAS来准宿主防御.
科学领域:
- 病毒学
- 细胞生物学
- 免疫学
背景情况:
- 病毒操纵宿主细胞机械进行复制和免疫逃避.
- 众所周知,天花病毒有复杂的策略来克服宿主抗病毒防御.
- 脊髓灰质炎病毒破坏宿主免疫力的确切机制往往尚不清楚.
研究的目的:
- 识别干扰宿主抗病毒反应的病毒因素.
- 阐明天花病毒F17蛋白在调节宿主细胞信号中的作用.
- 了解天花病毒如何调节哺乳动物的拉皮素 (mTOR) 信号传递.
主要方法:
- 蛋白与蛋白相互作用研究以确定F17标.
- 对有或没有F17的天花病毒感染的宿主细胞反应的分析
- 免疫光显微镜可视化蛋白质局部化 (cGAS,STING,mTOR).
- 对干扰素刺激的基因表达进行评估.
主要成果:
- 脊髓灰质炎病毒F17蛋白与mTORC1和mTORC2的关键调节者Raptor和Rictor结合并隔离.
- F17 破坏了对抗病毒反应至关重要的 mTORC1- mTORC2 交叉通话.
- 缺少F17的小病毒会触发cGAS-STING通路的激活,从而导致干扰素的产生.
- 表达F17的病毒导致mTOR失调,Golgi局部化和mTOR依赖的cGAS降解,抑制抗病毒信号传递.
结论:
- 脊髓灰质炎病毒F17蛋白是抑制宿主细胞核DNA传感的关键毒性因子.
- 通过F17对mTOR信号的调节失调是一种保存的天花病毒策略,以逃避天生的免疫力.
- 这种机制使得病毒能够抑制抗病毒反应,同时保持有益的mTOR活性.
相关概念视频
02:02Cis-regulatory Sequences
11.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.9K
02:02Cis-regulatory Sequences
4.2K
4.2K
02:57The Sense of Self: Reflected Self-Appraisal and Social Comparison
56.1K
According to Charles Cooley, we base our image on what we think other people see (Cooley 1902). We imagine how we must appear to others, then react to this speculation. We don certain clothes, prepare our hair in a particular manner, wear makeup, use cologne, and the like—all with the notion that our presentation of ourselves is going to affect how others perceive us. We expect a certain reaction, and, if lucky, we get the one we desire and feel good about it. But more than that, Cooley...
56.1K
01:28Global Regulatory Systems
692
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
692
01:26Introduction to Special Senses
7.6K
Sensory receptors play an integral part in comprehending our external and internal environments. They receive diverse stimuli, converting them into the nervous system's electrochemical signals. This conversion occurs as the stimulus alters the sensory neuron's cell membrane potential, instigating the generation of an action potential. This action potential is subsequently transmitted to the central nervous system (CNS), which integrates with other sensory data or higher cognitive...
7.6K
01:17Second-Order Circuits
3.6K
Integrating two fundamental energy storage elements in electrical circuits results in second-order circuits, encompassing RLC circuits and circuits with dual capacitors or inductors (RC and RL circuits). Second-order circuits are identified by second-order differential equations that link input and output signals.
Input signals typically originate from voltage or current sources, with the output often representing voltage across the capacitor and/or current through the inductor. For example, in...
Input signals typically originate from voltage or current sources, with the output often representing voltage across the capacitor and/or current through the inductor. For example, in...
3.6K