TRIM5α抑制了天花病毒,并受到CypA和病毒蛋白C6的对抗
Yiqi Zhao1,2, Yongxu Lu1,2, Samuel Richardson3
1Department of Pathology, University of Cambridge, Cambridge, UK.
Nature
|August 9, 2023
概括
人类TRIM5α (三方基因蛋白5α) 通过与其囊蛋白L3结合来限制正视病毒. 病毒蛋白C6和环素A可以抵消这种作用,
科学领域:
- 病毒学
- 免疫学
- 细胞生物学
背景情况:
- 人类三方基因蛋白5α (TRIM5α) 已知可以限制某些RNA病毒,如HIV.
- 它在限制DNA病毒,特别是骨病毒中的作用不太清楚.
研究的目的:
- 为了研究TRIM5α对骨病毒的抗病毒活性.
- 确定病毒对策和潜在的治疗点.
主要方法:
- 通过SPRY域与L3囊蛋白结合,证明了TRIM5α的限制.
- 鉴定出病毒蛋白C6和环素A (CypA) 作为对抗因素.
- 在体外评估了环素A (CsA) 和其衍生物 (alisporivir,NIM811) 的抗病毒作用.
主要成果:
- 通过与L3囊蛋白结合,抑制复制并激活先天免疫力,TRIM5α限制了骨病毒.
- 脊髓炎病毒使用C6来降解TRIM5α和CypA通过L3相互作用来对抗TRIM5α.
- CsA,阿里斯波里维尔和NIM811抑制了CypA,对依赖TRIM5α的骨病毒表现出抗病毒活性.
结论:
- TRIM5α 作为对骨病毒的限制因子.
- 病毒对策包括TRIM5α降解和CypA的对抗作用.
- 由于向宿主因子CypA,限制耐药性的出现,CsA衍生物显示为抗病毒疗法.
相关概念视频
Cytotoxic T Cells-mediated Immune Response
971
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
971
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Mechanisms of Retrovirus-induced Cancers
5.1K
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.1K
Retroviruses
12.4K
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’...
12.4K


