HIV-1 Replication Benefits from the RNA Epitranscriptomic Code

Abstract

The effects of RNA methylation on HIV-1 replication remain largely unknown. Recent studies have discovered new insights into the effect of 2'-O-methylation and 5-methylcytidine marks on the HIV-1 RNA genome. As so far, HIV-1 benefits from diverse RNA methylations through distinct mechanisms. In this review, we summarize the recent advances in this emerging field and discuss the role of RNA methylation writers and readers in HIV-1 infection, which may help to find alternative strategies to control HIV-1 infection.

Keywords: HIV-1; RNA methylation; Readers; Writers.

Figure 1:. A schematic presentation of the impact of RNA methylations on HIV-1 life cycle.

The m6A writers (METTL3/14) add the methyl group to the HIV-1 RNA at N6-adenosine, while the m6A methylation erasers (ALKBH5/FTO) remove such methyl groups. m6A methylation readers (YTHDF1-3) bind to m6A-modified HIV-1 RNA to either enhance viral protein expression or inhibit reverse transcription. The m5C writer (NSUN2) adds the methyl group to the HIV-1 RNA at the C5 position of cytosine, which can be recognized by potential m5C readers to facilitate alternative splicing of HIV-1 transcripts and enhance viral protein expression. FTSJ3 methylates the HIV-1 RNA at the 2′ hydroxyl (2′-O) of the ribose moiety and helps HIV-1 to escape from innate immune recognition. The question marks (?) indicate that the erasers of m5C and 2′ -O-methylation remain to be discovered.