通过ICAM-1介导的Src信号通路在脑肌心炎病毒进入中起着关键作用
Ruiya Lian1,2,3,4, Xueer Dou1,2,3, Na Wang1,2,3
1Engineering Research Center of Key Technology and Industrialization of Cell-based Vaccine, Ministry of Education, Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
Journal of virology
|July 9, 2025
概括
脑肌心炎病毒 (EMCV) 通过激活ICAM-1-Src-Ezrin-Cav-1通路来入侵细胞,该过程涉及卡韦林介导的内细胞. 抑制这些宿主蛋白可以限制EMCV感染,提供潜在的治疗点.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 脑肌心炎病毒 (EMCV) 是一种具有广泛宿主范围的动物性病原体.
- 众所周知,EMCV细胞的进入涉及卡维林介导内细胞分裂 (CavME),但精确的分子机制尚未完全理解.
研究的目的:
- 为了阐明EMCV细胞进入的分子机制.
- 为了识别参与EMCV入侵的宿主因素和信号通路.
- 探索EMCV感染的潜在治疗点.
主要方法:
- 研究了Src激酶,Fyn激酶和Ezrin在EMCV复制和内部化中的作用,使用小干扰RNA和抑制剂.
- 在各种细胞系 (BHK-21,hCMEC/D3,PK15) 中检查了EMCV入侵,这些细胞系用Src,Ezrin或Cav-1 (siCav-1) 抑制剂治疗.
- 分析了ICAM-1和Src之间的相互作用,并评估了EMCV进入ICAM-1淘汰细胞的情况.
主要成果:
- 过度表达Src或Fyn激酶增强了EMCV的复制和扩散.
- 抑制Src,Fyn和Ezrin,或Cav-1,降低了EMCV内部化的调节.
- 在EMCV进入过程中证明了Src,Ezrin和Cav-1的顺序激活,这是一种在人类,子和猪细胞中保存的途径.
- 确定ICAM-1作为与Src相互作用的受体,调节其酸化并影响EMCV的进入.
- 在BHK-21细胞中,EMCV的进入取决于ICAM-1-Src-Ezrin-Cav-1通路.
结论:
- EMCV利用ICAM-1-Src-Ezrin-Cav-1信号通路通过CavME进入细胞.
- 这一途径在人类,仓鼠和猪细胞中得到保护,突出显示了其广泛的相关性.
- 针对这种途径的组件,如Src,Ezrin或ICAM-1,为开发针对EMCV的抗病毒疗法提供了一个有希望的战略.
更多相关视频
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
Immunoglobulin-like Cell Adhesion Molecules
3.4K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.4K
Receptor-mediated Endocytosis
6.4K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
6.4K
C4 Pathway and CAM
46.3K
Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
C4 Pathway
The C4 pathway is used by plants such as...
46.3K
Enzyme-linked Receptors
80.1K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
80.1K
MAPK Signaling Cascades
6.2K
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...
6.2K


