Decombe Alice, Peersen Olve, Decroly Etienne
Architecture et Fonction des macromolécules biologiques, Centre national de la recherche scientifique, Aix-Marseille Université, Marseille 13288, France.
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
Virologie (Montrouge). 2024 Aug 1;28(4):277-293. doi: 10.1684/vir.2024.1056.
HIV-1 polymerase, commonly known as HIV reverse transcriptase (RT), catalyzes the critical reaction of reverse transcription by synthesizing a double-stranded DNA copy of the viral genomic RNA. During the replication cycle, this synthesized DNA is integrated into the host genome. This entire process is essential for viral replication and is targeted by several antiviral drugs. Numerous studies in biochemistry and structural biology have led to a good understanding of HIV-1 RT functions. However, the discovery of epitranscriptomic marks, such as 2'-O-methylations, on the HIV-1 RNA genome raise the questions about RT's ability to copy RNAs decorated with these biochemical modifications. This review focuses on the importance of RT in the viral cycle, its structure and function and the impact of 2'-O-methylations on its activity and replication regulation, particularly in quiescent cells.
HIV-1聚合酶,通常称为HIV逆转录酶(RT),通过合成病毒基因组RNA的双链DNA拷贝来催化逆转录的关键反应。在复制周期中,这种合成的DNA被整合到宿主基因组中。整个过程对于病毒复制至关重要,并且是几种抗病毒药物的作用靶点。生物化学和结构生物学方面的大量研究使人们对HIV-1 RT的功能有了很好的理解。然而,在HIV-1 RNA基因组上发现表转录组标记,如2'-O-甲基化,引发了关于RT复制带有这些生化修饰的RNA的能力的问题。本综述重点关注RT在病毒周期中的重要性、其结构和功能以及2'-O-甲基化对其活性和复制调控的影响,特别是在静止细胞中的影响。