核膜蛋白SUN2通过NS1介导的调节细胞骨架重组来促进病毒的复制
Yanxia Huang1,2,3, Qinyu Peng1,2, Xu Tian1,2
1Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
Nature communications
|January 4, 2024
概括
核蛋白SUN2对于病毒复制至关重要,包括寨卡病毒 (ZIKV) 和登革热病毒 (DENV). SUN2通过将细胞骨与细胞核连接起来,促进病毒RNA合成,从而影响病毒感染.
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:
- 病毒,包括寨卡病毒 (ZIKV),登革热病毒 (DENV) 和日本脑炎病毒 (JEV),在感染期间广泛利用宿主细胞细胞骨架.
- 弗拉维病毒与细胞骨相互作用和操纵的精确机制,特别是与细胞核的连接,仍然不完全理解.
研究的目的:
- 研究核膜蛋白质,特别是SUN1和SUN2在病毒复制中的作用.
- 阐明SUN2在弗拉维病毒感染期间影响病毒RNA合成和细胞骨重组的分子机制.
主要方法:
- 在宿主细胞中SUN1和SUN2的CRISPR/Cas9介导基因淘汰.
- 评估ZIKV,DENV,JEV和非病毒类RNA病毒的病毒复制水平.
- 使用主导负Nesprin构造研究蛋白质-蛋白质相互作用.
- 在新生儿小鼠模型中评估病毒复制和神经病理学.
主要成果:
- SUN2淘汰赛显著减少了ZIKV,DENV和JEV的复制,而SUN1淘汰赛没有显著的影响.
- 由于SUN2的前期病毒活动需要其三个功能区域.
- SUN2促进了细胞骨的重新排列和复制器官的形成,促进了病毒RNA合成.
- SUN2对于细胞骨活性蛋白和ZIKV非结构蛋白1 (NS1) 之间的相互作用至关重要.
- 通过纳斯来破坏SUN2-细胞骨连接,减少了病毒复制.
- 在新生小鼠中,SUN2淘汰赛极大地减少了体内ZIKV复制和神经病理.
结论:
- 通过协调细胞骨蛋白质的招募,SUN2在病毒复制中发挥着关键的,前期的作用.
- 核膜蛋白SUN2作为细胞骨和核骨之间的关键环节,促进了病毒感染.
- SUN2和纳斯普林是宿主对黄病毒感染反应的关键调解者,突出了一个新的治疗点.
更多相关视频
相关概念视频
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Protein Complex Assembly
10.6K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.6K
Intracellular Movement of Viruses and Bacteria
2.8K
Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a...
2.8K
Mechanisms of Retrovirus-induced Cancers
5.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K
Pinching-off of Coated Vesicles
3.2K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.2K


