通过ApoER2介导的Semliki森林病毒进入的分子基础
Bingchen Du1, Xiyong Song2, Bingyu Zhao1
1State Key Laboratory for Animal Disease Control and Prevention & Data Center for Field Scientific Observation and Research of Animal Diseases, Ministry of Agriculture and Rural Affair, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, PR China.
Nature communications
|December 19, 2025
概括
塞姆利基森林病毒 (SFV) 使用阿波利波蛋白E受体2 (ApoER2) 进入细胞,特别是通过其LA5域与SFV E1-DIII蛋白结合. 这一发现为中和SFV感染提供了一个新的目标.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 塞姆利基森林病毒 (SFV) 使用细胞受体进入.
- 非常低密度脂蛋白受体 (VLDLR) 和脂蛋白E受体2 (ApoER2) 是已知的SFV入口受体.
- 通过ApoER2调解的SFV进入的确切机制尚未完全理解.
研究的目的:
- 通过ApoER2阐明SFV通过ApoER2进入的分子机制.
- 为了确定参与SFV结合的ApoER2的特定域.
- 探索针对SFV-ApoER2相互作用的潜在治疗策略.
主要方法:
- 进行了生物化学分析和细胞实验.
- 低温电子显微镜 (cryo-EM) 用于确定复杂的结构.
- 用局部定向的突变发生法来验证关键相互作用.
主要成果:
- ApoER2 异型1 的 LA5 域与 SFV E1-DIII 特别结合.
- 这种相互作用通过一个小的接口 (353 Å2) 发生,并调解病毒细胞的附着和进入.
- 突变发生证实了接口残留的重要性.
- 一种可溶性LA5诱受体有效中和了SFV感染并保护了小鼠.
结论:
- 通过ApoER2输入的SFV依赖于LA5域,而不是VLDLR介导的输入.
- LA5域代表了对抗SFV的抗病毒干预的关键目标.
相关概念视频
Leaky 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
Retrovirus Life Cycles
49.1K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
49.1K
Receptor-mediated Endocytosis
7.4K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
7.4K
Initiation of Translation
38.2K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
38.2K


