在免疫受损的宿主中,SARS-CoV-2 的演变揭示了共享的中和逃生机制
Sarah A Clark1, Lars E Clark1, Junhua Pan1
1Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|April 8, 2021
概括
SARS-CoV-2 尖端蛋白 RBD 的突变可以帮助病毒逃避常见的抗体反应. 这些发现对于了解点蛋白向疫苗和治疗的长期有效性至关重要.
科学领域:
- 病毒学
- 免疫学
- 结构生物学
背景情况:
- 个体对SARS-CoV-2产生类似的抗体反应.
- 病毒尖端 (S) 蛋白的受体结合域 (RBD) 是中和抗体的关键目标.
- 了解对常见免疫反应的病毒进化对于开发有效的对策至关重要.
研究的目的:
- 调查SARS-CoV-2 RBD如何在常见抗体反应的免疫压力下演变.
- 识别对中和抗体产生抗性的特定突变.
- 评估这些突变对针对S的对策有效性的影响.
主要方法:
- 在持续感染的免疫受损个体中研究病毒进化.
- 使用抗体Fab/RBD结构分析来预测抗性突变.
- 采用伪型测试来确认被发现突变所赋予的抗体耐药性.
- 对康复期捐赠者的抗体和临床使用的单克隆抗体进行了耐药性测试.
主要成果:
- 鉴定出晚期S蛋白RBD突变,使其对一种常见的SARS-CoV-2中和抗体产生抗性.
- 对多个健康捐赠者的多克隆血清以及对临床相关的单克隆抗体的耐药性已被证明.
- 发现亲和力成熟对于野生型病毒中和并不重要,但对于中和范围至关重要.
结论:
- 在演化后的SARS-CoV-2变种中发现的突变可以对广泛中和抗体产生抗性.
- 这些发现预测了抗体耐药变体的出现,并对针对SARS-CoV-2尖端蛋白的疫苗和治疗方法的长期有效性产生了重大影响.
- 这项研究强调了病毒进化与宿主免疫反应之间的动态相互作用.
更多相关视频
14:23A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
15.9K
10:25Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
5.0K
相关概念视频
Viral Mutations
36.8K
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...
36.8K
Immune Response Against Viral Pathogens
1.2K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.2K
Single Nucleotide Polymorphisms-SNPs
17.2K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
17.2K
Viral Recombination
24.3K
Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
24.3K
Diversity of Antigen Receptors
1.1K
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
1.1K
Antigens Involved in Adaptive Immunity
889
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
889
