出口因子1/XPO1核出口途径抑制对冠状病毒复制的影响
Masmudur M Rahman1,2,3, Bereket Estifanos2,4, Honor L Glenn3,4
1Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Viruses
|February 26, 2025
概括
使用Selinexor抑制XPO1 (出口因1) 途径增强了小鼠肝炎病毒的复制. 这条路径的路径.
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:
- 通过XPO1 (出口因1) 进行核细胞质运输对细胞功能至关重要.
- 病毒劫持XPO1进行复制,使其成为治疗目标.
- 选择性XPO1抑制剂如Selinexor可能会影响病毒动态.
研究的目的:
- 为了研究XPO1抑制对冠状病毒复制的影响.
- 为了确定Selinexor是否对MHV和SARS-CoV-2表现出抗病毒或前病毒活性.
主要方法:
- 使用Selinexor,这是FDA批准的XPO1抑制剂.
- 采用培养的人类和小鼠细胞系.
- 评估病毒蛋白表达和复制水平.
- 进行了XPO1蛋白倒置实验.
主要成果:
- 塞林克索前期治疗显著增强了小鼠肝炎病毒 (MHV) 复制和细胞培养中的蛋白质表达.
- 击败XPO1也增加了人类细胞中的MHV复制.
- 塞林克索对不同细胞类型的SARS-CoV-2复制产生了不同的影响.
结论:
- 抑制XPO1可以增强冠状病毒的复制,特别是MHV.
- 抑制XPO1对病毒复制的影响取决于病毒和细胞类型.
- 准XPO1可能对病毒感染有复杂的影响.
相关概念视频
Nuclear Export
3.6K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
Nuclear Export of mRNA
4.5K
4.5K
Directionality of Nuclear Transport
3.2K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.2K
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
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Export of Misfolded Proteins out of the ER
3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K


