MAVS化作为一种调节抗病毒免疫力的细胞应激传感器
Dongyi Zhao1,2, Nao Morimoto1, Riho Saito1,2
1Laboratory of Molecular Cell Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
iScience
|August 21, 2025
概括
细胞应激通过促进MAVS酸化来增强抗病毒免疫力,这是RIG-I类受体信号传递的一个关键步骤. 这将压力途径与I型干扰素的产生联系在一起,从而促进对病毒感染的先天免疫反应.
科学领域:
- 免疫学
- 分子生物学
- 病毒学
背景情况:
- 细胞体RIG-I类受体 (RLR) 检测病毒RNA,通过MAVS启动先天免疫反应.
- MAVS信号导致I型干扰素 (IFN) 的产生和亡,这对抗病毒防御至关重要.
- 细胞应激对MAVS介导的抗病毒免疫力的影响尚不清楚.
研究的目的:
- 研究细胞应激在调节MAVS信号和I型IFN产生中的作用.
- 阐明细胞应激与MAVS依赖的抗病毒免疫的分子机制.
主要方法:
- 由ASK1激活的p38 MAPK对MAVS的酸化进行了研究.
- 评估了MAVS与TRAF适应蛋白的相互作用.
- 在各种压力条件下 (氧化,ER压力) 使用野生型和突变MAVS对病毒感染的反应分析了I型IFN表达.
主要成果:
- 由ASK1激活的p38 MAPK介导的MAVS酸化增强了MAVS- TRAF相互作用.
- 细胞应激 (氧化,ER) 显著放大病毒诱导的I型IFN表达.
- 这种压力诱导的放大取决于MAVS酸化位点.
结论:
- MAVS酸化是将细胞应激信号整合到抗病毒先天免疫中的关键机制.
- 通过MAVS酸化,MAPK途径作为细胞应激传感器调节抗病毒反应.
- 在受细胞应激水平影响的情况下,MAVS化微调抗病毒免疫力.
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.6K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.6K
Immune Response Against Viral Pathogens
917
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...
917
MAPK Signaling Cascades
6.0K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.0K
PI3K/mTOR/AKT Signaling Pathway
3.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.9K
The JAK-STAT Signaling Pathway
9.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.2K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K


