肠道病毒71激活储存进入和线粒体呼吸是有效复制病毒的必要条件
Bang-Yan Hsu1, Ya-Hui Tsai2, Ta-Chou Weng1
1Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
mBio
|July 8, 2025
概括
肠道病毒71 (EV71) 通过通过STIM1和Orai1激活储存的Ca2+输入 (SOCE) 来劫持细胞 (Ca2+) 信号. 这个过程推动病毒复制,促进细胞死亡,帮助病毒释放.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 信号传递 信号传递
背景情况:
- 肠道病毒 (EV) 感染破坏细胞 (Ca2+) 稳态,影响病毒生命周期.
- 在EV感染,特别是EV71期间细胞溶液Ca2+增加的确切机制尚不清楚.
- EV蛋白2B定位到ER,导致Ca2+储存物耗尽,随后发生细胞外Ca2+涌入.
研究的目的:
- 为了阐明在EV71感染期间Ca2+流入的机制.
- 为了研究在EV71复制中存储的Ca2+输入 (SOCE) 的作用.
- 探索改变Ca2+信号对病毒病变和宿主细胞命运的下游影响.
主要方法:
- 同焦点成像可视化感染细胞中的STIM1和Orai1定位.
- 药物抑制和STIM1和Orai1.1的遗传淘汰 (siRNA) 的药物抑制和遗传淘汰.
- 全球转录组分析以确定差异表达的基因.
- 鼠标肠道有机体培养物以评估生理模型中的病毒复制.
主要成果:
- EV71感染通过诱导STIM1激活和其与Orai1在血上的相互作用来激活SOCE.
- 抑制或淘汰STIM1/Orai1显著降低细胞质Ca2+水平和病毒复制.
- SOCE的激活调高了线粒体电子运输链 (ETC) 的活性,增强了ATP的产生.
- 线粒体Ca2+的增加导致细胞亡,并促进病毒的释放.
结论:
- EV71利用由STIM1-Orai1介导的SOCE来操纵宿主Ca2+信号进行复制.
- 线粒体Ca2+过载有助于EV71诱导的亡和病毒释放.
- STIM1和Orai1代表了针对EVs的广泛抗病毒策略的潜在治疗点.
相关概念视频
Feedback Regulation of Calcium Concentration
3.5K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.5K
Mitochondrial Membranes
12.4K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.4K
Intracellular Movement of Viruses and Bacteria
2.9K
Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a...
2.9K
Porin Insertion in the Outer Mitochondrial Membrane
3.3K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.3K
Protein Transport into the Inner Mitochondrial Membrane
4.1K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
4.1K
Overview of Secretory Vesicles
8.7K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.7K


