爱斯坦-巴尔病毒BALF0/1颠覆了Caveolin和ERAD通路,以向B细胞受体复合体进行降解
Stephanie Pei Tung Yiu1,2,3,4, Yifei Liao1,3,4, Jinjie Yan1,3,4
1Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
概括
爱斯坦-巴尔病毒蛋白BALF0/1在溶性复制过程中降解B细胞受体,阻断信号传递并帮助维释放. 这一发现揭示了病毒的持续性和相关疾病.
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:
- 爱斯坦-巴尔病毒 (EBV) 导致持续性感染,传染性单核病,并与多发性硬化和癌症有关.
- 了解EBV如何重塑宿主B细胞以进行溶性复制至关重要,但不完整.
- 之前的研究表明,EBV溶性复制消耗了血B细胞受体 (BCR) 复合体.
研究的目的:
- 为了识别EBV蛋白质,负责在化周期期间BCR降解.
- 阐明EBV针对BCR复合物的降解机制.
- 调查EBV对BCR下调的功能后果.
主要方法:
- 用蛋白质和生化分析来识别病毒蛋白并研究其相互作用.
- 使用CRISPR-Cas9创建了BALF0/1淘汰 EBV菌株.
- 细胞活力测试是在扩散的大B细胞淋巴瘤细胞系上进行的.
主要成果:
- 鉴定出EBV早期溶解蛋白BALF0/1是BCR降解的关键调解者.
- BALF0/1使用免疫球蛋白重链KVK基因进行无素介导的降解,独立于CD79A/B.
- 该病毒颠覆了卡韦林介导的内细胞分裂和与ER相关的降解途径.
- BALF0/1淘汰赛降低了病毒载量,并增加了免疫球蛋白纳入病毒颗粒.
- 过度表达BALF0/1降低了依赖BCR的淋巴瘤细胞的活力.
结论:
- 在Lytic反应过程中EBV BALF0/1降低免疫球蛋白,以抑制BCR信号传递.
- 这一过程促进了病毒的释放,并可能导致EBV相关的病理.
- 需要进一步的研究来探索EBV的活体活性作用.
更多相关视频
08:44Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
2.4K
12:48Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
8.2K
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
Receptor-mediated Endocytosis
103.9K
Overview
103.9K
Intralumenal Vesicles and Multivesicular Bodies
3.4K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.4K
Cross-reactivity
30.9K
Overview
30.9K
B Cell Activation and Differentiation
1.6K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.6K
ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
