病毒通过Nrf2途径调节ROS动态,以促进病毒复制
Honghui He1,2,3, Kai Yuan4, Junming Pan1,2,3
1State Key Laboratory of Biocontrol, School of Marine Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|March 17, 2025
概括
白斑综合征病毒 (WSSV) 操纵了.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 水产养殖 免疫学 免疫学
背景情况:
- 反应性氧物种 (ROS) 对于宿主防御和细胞信号传递至关重要.
- 病毒通常会操纵宿主ROS稳态,以确保它们的复制.
- 病毒改变ROS动态的机制在很大程度上是未知的.
研究的目的:
- 阐明白斑综合症病毒 (WSSV) 调节 (Litopenaeus vannamei) 中ROS稳态的分子机制.
- 为了研究WSSV如何通过操纵宿主抗氧化途径来增强其复制.
主要方法:
- 研究了WSSV蛋白 wsv220与核因子红色素2相关因子2 (LvNrf2) 途径组件 (LvKeap1) 之间的相互作用.
- 分析了LvNrf2激活对抗氧化基因表达 (例如,LvG6PDH) 和ROS水平的影响.
- 利用基因淘汰技术来评估LvNrf2和LvG6PDH在WSSV复制中的作用.
主要成果:
- WSSV 蛋白 wsv220 破坏了 LvNrf2/LvKeap1 复合体,促进了 LvNrf2 核转位.
- 激活的LvNrf2上调抗氧化基因,增加NADPH和GSH以减少ROS并支持病毒复制.
- WSSV建立了一个积极的反循环,涉及wsv051以进一步增强wsv220表达和病毒复制.
- 抑制LvNrf2或LvG6PDH抑制了WSSV的复制,并提高了宿主ROS水平.
结论:
- WSSV劫持了的LvNrf2通路,以维持ROS恒温,为病毒复制创造了有利的环境.
- 涉及病毒基因的积极反循环促进了WSSV的扩散.
- 向LvNrf2通路为养殖中的WSSV提供了潜在的抗病毒策略.
相关概念视频
Regulation of Nuclear Protein Sorting
2.3K
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...
2.3K
Experimental RNAi
6.0K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.0K
Leaky Scanning
5.0K
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...
5.0K
siRNA - Small Interfering RNAs
16.4K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.4K
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
The Unfolded Protein Response
4.3K
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...
4.3K


