人类细胞巨头病毒编码的G蛋白结合受体 (GPCR),UL78,调节病毒的重新激活
bioRxiv : the preprint server for biology
|June 12, 2025
概括
人类细胞巨型病毒 (CMV) 蛋白UL78对于病毒从潜伏状态的重新激活至关重要. UL78重塑了细胞信号,将环境从有利于延迟转变为支持重新激活和潜在的疾病.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 人类细胞巨乳病毒 (CMV) 在造血细胞中建立了终身潜伏期.
- 病毒重新激活发生在免疫失调期间,导致疾病.
- 在潜伏期间,CMV蛋白US28和UL78表达,US28对维持其至关重要.
研究的目的:
- 调查CMV蛋白UL78在病毒再激活中的作用.
- 了解US28和UL78相互作用如何影响宿主细胞在重新激活期间的信号传递.
- 阐明CMV从潜伏状态转变为溶解状态的机制.
主要方法:
- 在髓状细胞中利用UL78ORF删除突变体.
- 分析了病毒延迟和重新激活效率.
- 评估宿主细胞信号通路,包括ERK酸化.
- 在US28和UL78.8.之间研究了蛋白质与蛋白质的相互作用.
主要成果:
- 需要UL78才能有效地从髓状细胞中激活CMV.
- UL78影响细胞信号,促进从延迟到重新激活的切换.
- 缺乏UL78的病毒感染细胞的重新激活显示了ERK酸化的减少.
- 在分化过程中,US28和UL78在髓状细胞中相互作用和局部化.
结论:
- UL78通过调节宿主细胞信号传递,在CMV的再激活中起着至关重要的作用.
- UL78:US28相互作用对于在重新激活时改变US28介导的信号传输很重要.
- UL78代表了一种新的治疗点,用于预防CMV的重新激活和相关疾病.
相关概念视频
Receptor Downregulation in MVBs
2.0K
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...
2.0K
Immune Response Against Viral Pathogens
764
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...
764
GPCRs Regulate Adenylyl Cylase Activity
5.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.3K
GPCR Desensitization
5.9K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.9K


