人类疹病毒8病毒性干扰素调节因子4与乌比奎丁特异性蛋白酶7的生物学显著相互作用
1Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Journal of virology
|May 16, 2024
概括
人类疹病毒8 (HHV-8) vIRF-4蛋白需要USP7才能获得最佳的表达和复制. 这种相互作用通过抑制TRAF3,帮助HHV-8感染来抑制天生的免疫力.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 人类疹病毒8 (HHV-8) 编码针对宿主细胞防御机制的病毒干扰素调节因子 (vIRF).
- vIRFs 1-3与全素特异蛋白酶7 (USP7) 相互作用,影响病毒复制和细胞存活.
- 在HHV-8感染中vIRF-4与USP7相互作用的功能意义尚不清楚.
研究的目的:
- 阐明在HHV-8中vIRF-4和USP7相互作用的生物学意义.
- 研究这种相互作用在病毒复制和宿主免疫逃避中的作用.
- 确定vIRF-4作为TRAF3的调节剂及其对先天免疫力的影响.
主要方法:
- 在受感染细胞中的vIRF-4-USP7相互作用的遗传消去.
- 对vIRF-4无处不在和表达的分析.
- 评估I型干扰素 (IFN-I) 诱导和信号通路.
- 调查TRAF3激活及其通过vIRF-4和USP7.7.的调节.
主要成果:
- 与USP7的vIRF-4关联对于最佳的vIRF-4表达和HHV-8复制至关重要.
- 结合USP7抑制了vIRF-4的泛化,导致vIRF-4水平增加.
- vIRF-4以USP7依赖的方式抑制TRAF3激活,从而导致先天性免疫抑制.
- 这种相互作用对于HHV-8逃避宿主抗病毒反应的能力至关重要.
结论:
- 这项研究揭示了vIRF无化和USP7基质的第一个实例.
- 通过与USP7.7的相互作用,vIRF-4表达和HHV-8复制得到增强.
- 通过TRAF3调节,vIRF-4抑制了先天免疫力,这是一种新的病毒免疫规避策略.
- 针对vIRF-4-USP7相互作用可以提供针对HHV-8感染的新治疗途径.
相关概念视频
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
Export of Misfolded Proteins out of the ER
3.6K
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...
3.6K
Immune Response Against Viral Pathogens
776
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...
776
The Unfolded Protein Response
4.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.6K
Regulation 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


