核酸的SUMOylation依赖性降解是导致Pestivirus脱涂的原因
Lin-Ke Zou1, Ji-Shan Bai1, Rui-Cong Sun2
1MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Journal of virology
|November 25, 2025
概括
经典猪瘟病毒 (CSFV) 的脱涂依赖于一种新的SUMOylation-dependent途径. 主体蛋白VCP针对病毒核心蛋白进行蛋白质体降解,促进基因组释放并提供新的抗病毒点.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 经典猪瘟病毒 (CSFV) 是一个重要的杀虫病毒病原体.
- 病毒脱涂机制对于感染至关重要,尚未完全理解.
- 在脱涂过程中,CSFV核心蛋白质至关重要.
研究的目的:
- 阐明控制CSFV脱涂的分子机制.
- 为了确定参与CSFV体分解和基因组释放的宿主因素.
- 为了探索潜在的抗病毒目标在杀虫病毒属.
主要方法:
- 研究了CSFV核心蛋白和宿主因子之间的相互作用.
- 利用位点定向突变发生来评估SUMOylation的作用.
- 采用CSFV病毒的光追踪和VCP耗尽研究.
主要成果:
- 发现由宿主含有氨酸的蛋白质 (VCP/p97) 降解CSFV核心蛋白的SUMOylation-依赖,无素-独立的降解.
- 通过PSMB2和PSMD2子单元,VCP调解了Core的蛋白质体降解.
- VCP 调节病毒贩运到晚期内基因组的过程,这对于囊分解和基因组释放至关重要.
结论:
- 一个新的SUMO1-VCP-PSMB2/PSMD2轴通过将细胞内贩运与蛋白质体分解相结合来调节CSFV脱涂.
- 这项研究提供了第一个证据,表明SUMOylation与病毒脱涂有关.
- 参与这种途径的宿主因素代表了疫苗病毒的有希望的抗病毒标.
相关概念视频
01:32Pinching-off of Coated Vesicles
4.0K
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...
4.0K
02:41Protein Complex Assembly
16.5K
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...
16.5K
02:27Nonsense-mediated mRNA Decay
11.7K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
11.7K
02:27Nonsense-mediated mRNA Decay
3.2K
3.2K
02:28Leaky Scanning
5.6K
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...
5.6K
01:45Regulation of Nuclear Protein Sorting
3.2K
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...
3.2K