SARS-CoV-2 S,M 和 E 结构性葡萄糖蛋白差异调节内细胞网膜应激反应的应激反应
Wejdan Albalawi1,2, Jordan Thomas1, Farah Mughal1
1Department of Clinical Infection, Microbiology and Immunology (CIMI), Institute of Infection, Veterinary and Ecological Sciences (IVES), University of Liverpool, Liverpool L69 7BE, UK.
International journal of molecular sciences
|February 13, 2025
概括
在SARS-CoV-2中,S,M和E结构蛋白通过破坏NF-κB信号来降低HIV-1LTR活性. 这会影响干扰素刺激的基因和内分泌网膜应激通路,影响因病毒变异而有所不同.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 型肝炎病毒 (HCV) E1E2 糖蛋白破坏NF-κB的激活,并上调细胞内膜网膜 (ER) 的压力.
- 了解其他病毒蛋白如何调节宿主细胞通路对于疾病研究至关重要.
研究的目的:
- 研究SARS-CoV-2结构蛋白 (S,M,E,N) 对HIV-1长端重复 (LTR) 活性的影响.
- 分析与SARS-CoV-2结构蛋白表达相关的基因表达变化及其与细胞应激通路的关系.
主要方法:
- 利用伪型病毒颗粒 (PVP) 来创建表达SARS-CoV-2结构蛋白的细胞系.
- 对表达S,M,E或N蛋白质的细胞进行了差异基因表达分析 (DGEA).
- 评估了HIV-1 LTR活性和NF-κB信号的调节.
主要成果:
- SARS-CoV-2 S,M和E蛋白,但不是N,剂量依赖下调的HIV-1 LTR活性.
- 武汉S菌株的效果最高,其后变种的影响较小 (Omicron最弱).
- 观察到干扰素刺激基因 (ISG) 和热冲击蛋白 (HSP) 基因的升调,以及转录因子模式的改变 (SP1,MAVS).
结论:
- SARS-CoV-2 的结构蛋白,特别是包膜糖蛋白,可以激活 ER 应激通路并破坏 NF-κB 信号传递.
- SARS-CoV-2 感染调节细胞通路,影响受感染细胞中的生理反应.
- 基因表达的变化表明细胞对SARS-CoV-2结构蛋白表达的广泛反应.
相关概念视频
01:31Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
01:17Role of ER in the Secretory Pathway
5.2K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.2K
01:29Protein Folding Quality Check in the RER
3.7K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.7K
01:26Protein Modifications in the RER
5.0K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.0K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
7.1K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.1K
01:32Export of Misfolded Proteins out of the ER
3.5K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.5K