葡萄糖为燃料的基斯修饰驱动HIV-1潜伏逆转在低氧
bioRxiv : the preprint server for biology
|September 26, 2025
概括
葡萄糖的可用性对于在低氧条件下逆转HIV-1潜伏期至关重要. 过高血糖会增强病毒储库的重新激活,揭示HIV-1治愈策略的代谢标.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 代谢研究研究 代谢研究
背景情况:
- CD4 T 细胞中持久的HIV-1 潜伏储存是治愈HIV感染的主要障碍,在抗逆转录病毒疗法 (ART) 中断后引起病毒反弹.
- 目前使用延迟逆转剂 (LRA) 的策略受到组织环境中延迟逆转机制的不完全理解的限制.
研究的目的:
- 调查代谢因素,特别是葡萄糖和氧气的可用性,在HIV-1潜伏逆转中的作用.
- 在生理学上相关的条件下识别差异性LRA疗效的分子决定因素.
主要方法:
- 采用药理学和代谢学方法来模拟体内发现的葡萄糖和氧气变异.
- 在不同的代谢条件下,评估了主要LRA类,PKC激活剂 (PKCags) 和基因素脱乙酶抑制剂 (HDACis) 的疗效.
- 研究了LRA诱导的葡萄糖分解,基因素乳酸和艾滋病毒促进体的染色质可访问性之间的机制联系.
主要成果:
- 葡萄糖被确定为HIV-1潜伏逆转的条件必需营养素,特别是在缺氧的情况下.
- 发现高血糖状况有助于增强HIV-1潜伏逆转.
- 在限制葡萄糖的条件下,PKCags和HDACis表现出不同的疗效,这与它们对糖溶性流量的差异诱导有关.
- 通过PKCag诱导的糖解促进了基因组乳化,这是一个与延迟逆转和增加染色质可访问性相关的翻译后修饰.
- 鉴定出KAT2A是一种关键的乳酸转移酶,用于延迟逆转相关的组分激素乳化.
结论:
- 葡萄糖和氧气的可用性是影响HIV-1潜伏逆转的关键代谢决定因素.
- 研究结果强调了体外建模的重要性,该建模反映了在体内有效的治疗剂的生理条件,以准潜伏的HIV-1储存库.
相关概念视频
Size and Structure of Viral Genomes
691
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...
691
Histone Modification
4.4K
4.4K
Histone Modification
15.9K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
15.9K
Chromatin Modification in iPS Cells
2.1K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.1K
Glucose Homeostasis: Regulation of Blood Glucose
3.9K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
3.9K
Spreading of Chromatin Modifications
9.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
9.3K


