在GII.4中的功能多样性 诺罗病毒进入:HBGA结合和囊集群动力学
bioRxiv : the preprint server for biology
|June 6, 2025
概括
人类诺罗病毒GII.4变种表现出不同的细胞进入机制. 由特定的VP1残留物驱动的集群变异显示出增强的膜受伤和内细胞分裂,影响病毒复制和治疗发展.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 胃肠病学 胃肠病学
背景情况:
- 人类诺病毒 (HuNoVs),特别是GII.4菌株,是全球病毒性胃肠炎的主要原因.
- 目前的治疗选择,包括疫苗和抗病毒药物,对于HuNoVs.是有限的.
- GII.4 Sydney的细胞进入机制涉及膜受伤和CLIC介导的细胞内,但其跨变体的保存是未知的.
研究的目的:
- 为了研究人类诺罗病毒GII.4变种保存的细胞进入机制.
- 为了比较不同GII.4菌株的早期结合和进入过程.
- 为了确定关键的病毒因素和宿主细胞过程,涉及GII.4诺罗病毒细胞进入.
主要方法:
- 使用野生型和突变GII.4病毒样颗粒 (VLPs) 进行比较分析.
- 采用修饰的人类肠肠菌体 (HIE) 培养物来模拟肠细胞感染.
- 进行了针对宿主细胞通路的抑制剂研究,并分析了VLP突变.
主要成果:
- 只有GII.4变异的一个子集在细胞表面形成了明显的,依赖于HBGA的囊集群.
- 与非集群变体相比,集群变体显示显著增强了膜受伤和内细胞分裂.
- 特定的VP1残留物 (V333和R339) 被确定为关键的集群和入口,独立于HBGA结合.
- 聚类和内细胞分裂是由脂质重塑驱动的,由胆固醇和胺调节,而不是宿主蛋白质糖化.
- 在GII.4变体中观察到聚类 (高入门能力) 和非聚类表型之间的二分法.
结论:
- 细胞进入机制在GII.4诺罗病毒变体之间有所不同,聚类是进入能力的关键决定因素.
- 特定的VP1残留物介于聚类和随后的膜相关进入过程.
- 了解这些菌株特异性机制,可以深入了解诺罗病毒病原和潜在的治疗点.
相关概念视频
Diversity of Antigen Receptors
1.4K
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...
1.4K
Viral Structure
73.9K
Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
73.9K
Size and Structure of Viral Genomes
704
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
704
Viral Recombination
24.9K
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.
24.9K
Glycocalyx and its Functions
8.0K
The glycocalyx is a carbohydrate-rich, fuzzy-appearing layer on the outer surface of the cell membrane. It is highly hydrophilic, because of this it attracts large amounts of water to the cell's surface. This aids the cell's interaction with the watery environment and also helps it to obtain substances dissolved in the water. It is also important for cell identification, self/non-self determination, and embryonic development and is used in cell-to-cell attachments to form tissues.
8.0K
Vesicular Tubular Clusters
3.1K
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
3.1K


