HBV囊组装调节器差异调节野生类型和耐药核心蛋白质仿真核囊和空囊的组装
Hui Liu1, Hemraj Rimal1, Jun Lyu1
1Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America.
PLoS pathogens
|August 5, 2025
概括
体组合调节器 (CAM) 在治疗慢性乙型肝炎方面表现有前途. 即使少量野生型 (WT) 核心蛋白 (Cp) 也可以抑制CAMs,可能会减缓耐药乙型肝炎病毒 (HBV) 变种的出现.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 病毒学 病毒学
- 药物开发 药物开发
背景情况:
- 慢性乙型肝炎 (CHB) 治疗面临挑战,原因是新出现的耐药性乙型肝炎病毒 (HBV) 菌株.
- 囊组装调节器 (CAM) 是一种有前途的CHB治疗策略,但它们的有效性可能会受到抗性HBV变体的损害.
研究的目的:
- 研究CAMs如何调节涉及野生类型 (WT) 和CAM抗性HBV核心蛋白 (Cp) 的仿真囊组装和拆卸.
- 了解在抗病毒疗法下出现抗CAM抗性HBV变体的机制.
主要方法:
- 人类肝瘤细胞与WT和突变HBV复制体的同时感染,在不同比例下表达CAM耐药Cp.
- 在体外囊组装试验中,评估CAMs对仿真囊形成和拆卸的影响.
- 对不同CAM (AB-506和GLS4) 的化学核体组成和敏感性的分析.
主要成果:
- 只有10%的WT Cp的表达显著抑制了CAM介导核体组合.
- 使用T33N替代的Cp (50%) 对AB-506诱导的空组合产生了完全的抗性,但对GLS4.4仍然敏感.
- 在模拟核体中,大约50%的WT Cp是CAMs诱导成熟核体分解和抑制HBV感染所必需的.
结论:
- 由于CAMs破坏了HBV核体组合,因此只需要很小一部分Cp结合口袋参与.
- 通过CAMs诱导成熟核片分解,需要占用较大比例的Cp结合口袋.
- 在抑制核囊组合方面,WT Cp的优势可能会在治疗期间延迟抗CAM抗性HBV的出现.
相关概念视频
00:56Viral Structure
63.8K
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.
63.8K
02:41Protein Complex Assembly
10.9K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
10.9K
00:36Viral Mutations
32.9K
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...
32.9K
01:26Size and Structure of Viral Genomes
145
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...
145
02:28Leaky 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
02:33Retroviruses
12.7K
Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
12.7K