[When 2'-O-methylation throws a wrench in HIV-1 reverse transcriptase]

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.