多 (ADP-ribose) 聚合酶-1 调节人类 CD4+ T 细胞中的 HIV-1 复制
bioRxiv : the preprint server for biology
|June 25, 2024
概括
多 (ADP-ribose) 聚合酶-1 (PARP-1) 缺乏或抑制通过增加与病毒相关的Env. 这确定了PARP-1作为调节HIV-1复制和感染性的宿主因子.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 细胞过程可以抵消病毒复制,为感染控制提供点.
- 聚 (ADP-ribose) 聚合酶-1 (PARP-1) 在HIV-1感染中的作用是有争议的,之前的研究仅限于伪型病毒.
- 了解宿主-病原体相互作用对于开发抗病毒策略至关重要.
研究的目的:
- 研究PARP-1缺乏或抑制对人类CD4+T细胞HIV-1复制的作用.
- 阐明PARP-1影响HIV-1感染力和病毒产生机制.
- 确定PARP-1参与调节HIV-1的特定领域和活动.
主要方法:
- 使用PARP-1淘汰SUP-T1细胞和PARP-1抑制剂,以向DNA结合和催化活动.
- 进行了突变发生分析,以评估PARP-1域在抗HIV-1活性中的作用.
- 评估HIV-1复制,感染性和生产细胞和纯化的病毒中与病毒相关的Env水平.
- 研究了病毒Env在PARP-1对感染能力的影响中的作用,使用了Env删除的病毒.
主要成果:
- PARP-1淘汰和DNA结合抑制增强了HIV-1的复制和感染力.
- 针对PARP-1催化活性的抑制剂没有影响病毒复制.
- 突变检测证实了DNA结合域,而不是多ADP-ribosylation活性,对PARP-1的抗HIV-1功能至关重要.
- 在生产阶段PARP-1起作用,增加新产生的HIV-1的传染性.
- PARP-1 缺乏导致病毒相关Env增加,依赖于病毒Env,但不会改变生产细胞中的Env表达.
结论:
- PARP-1 反对作用增强了HIV-1 感染力,主要是通过增加与病毒相关的Env.
- PARP-1的DNA结合活性,而不是其催化活性,对于其抗HIV-1作用至关重要.
- PARP-1被确定为调节HIV-1感染性的宿主因子,这对理解病毒传播和疫苗开发有意义.
相关概念视频
Retrovirus Life Cycles
45.8K
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...
45.8K
RNA Polymerase II Accessory Proteins
9.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K
Negative Regulator Molecules
35.3K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.3K
S-Cdk Initiates DNA Replication
4.7K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.7K


