奈洛病毒聚合酶突变与人类细胞中持续感染的建立有关
Keisuke Ohta1, Naoki Saka1, Yuzuha Nishi1
1Department of Microbiology, School of Medicine, Wakayama Medical University, Wakayama, Japan.
Journal of virology
|February 15, 2024
概括
克里米亚-刚果出血热病毒 (CCHFV) 可以通过其L蛋白中的特定突变在人体细胞中持续存在,这些突变限制了病毒的生长并抑制了先天免疫力. 这项研究揭示了纳伊罗病毒在人类中的持续性的一个关键机制.
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:
- 克里米亚-刚果出血热病毒 (CCHFV) 是一种由传播的奈洛病毒,在细胞和非人类灵长类动物中产生持久感染.
- 奈洛病毒在人体细胞中实现持久感染的机制在很大程度上仍未被描述.
研究的目的:
- 研究人类细胞中持续性奈洛病毒感染的机制.
- 利用CCHFV的替代品哈扎拉脊髓炎病毒 (HAZV) 来在人类细胞系中建模持久感染.
主要方法:
- 建立了一个持续感染HAZV (HAZVpi) 的人类细胞系.
- 使用测序分析HAZVpi的L蛋白中的突变.
- 评估病毒生长率,聚合酶活性和病毒释放.
- 研究了突变对病毒持久性和先天免疫抑制的影响.
主要成果:
- 感染HAZVpi的细胞在培养超水生物中没有检测到的病毒.
- 在HAZVpi的L蛋白中发现了五种突变 (mut1-mut5).
- 突变Lmut1和Lmut4单独限制了病毒生长,但这被其他突变 (Lmut2,Lmut3,Lmut5) 补偿,使得病毒持续存在.
- HAZVpi感染抑制了宿主细胞中的天生的免疫力.
结论:
- 病毒L蛋白中的合作点突变对于在人体细胞中建立持久HAZV感染至关重要.
- 病毒抑制天生的免疫力有助于其持续存在.
- 这项研究提供了对人类细胞中nairovirus持久感染背后的分子机制的第一个见解.
相关概念视频
Viral Mutations
32.3K
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...
32.3K
Retrovirus Life Cycles
46.0K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.0K
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
12.3K
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’...
12.3K


