在protocadherin-1中发生的两点突变破坏了汉塔病毒的识别,并提供了对致命感染的保护
Megan M Slough1, Rong Li2, Andrew S Herbert3
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Nature communications
|July 24, 2023
概括
安第斯病毒和Sin Nombre病毒导致严重疾病,但宿主蛋白质Protocadherin-1 (PCDH1) 是一个新的目标. 针对汉塔病毒糖蛋白和PCDH1之间的相互作用,可能会导致汉塔病毒心肺综合征的新疗法.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 安第斯病毒 (ANDV) 和Sin Nombre病毒 (SNV) 在美洲引起汉塔病毒心肺综合征 (HCPS).
- 目前没有FDA批准的HCPS治疗方法.
- Protocadherin-1 (PCDH1) 是一种新发现的宿主因子,对ANDV和SNV感染至关重要,是潜在的抗病毒标.
研究的目的:
- 为了阐明PCDH1在汉塔病毒入侵中的确切作用.
- 划分汉塔病毒糖蛋白和PCDH1.1之间的结合接口.
- 探索PCDH1作为HCPS的治疗点.
主要方法:
- 计算建模用于预测结合表面.
- 蛋白质与蛋白质相互作用的实验验证.
- 在活体研究中,使用叙利亚仓鼠感染ANDV的模型.
主要成果:
- 确定了汉塔病毒糖蛋白在PCDH1第一个细胞外阴重复域上的结合表面.
- PCDH1中单个氨基酸突变会影响SNV宿主物种的特异性和细胞进入.
- 在PCDH1中的突变显著保护了子免受ANDV诱导的疾病和死亡.
结论:
- PCDH1作为ANDV和SNV的真诚进入受体.
- 针对汉塔病毒糖蛋白和PCDH1之间的相互作用,为开发新的HCPS干预提供了一个有希望的策略.
相关概念视频
Leaky Scanning
5.2K
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...
5.2K
Viral Mutations
32.4K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.4K


