Epitranscriptomic regulation of viral replication

RNA plays central roles in biology and novel functions and regulation mechanisms are constantly emerging. To accomplish some of their functions within the cell, RNA molecules undergo hundreds of chemical modifications from which N6-methyladenosine (m⁶A), inosine (I), pseudouridine (ψ) and 5-methylcytosine (5mC) have been described in eukaryotic mRNA. Interestingly, the m⁶A modification was shown to be reversible, adding novel layers of regulation of gene expression through what is now recognized as epitranscriptomics. The development of molecular mapping strategies coupled to next generation sequencing allowed the identification of thousand of modified transcripts in different tissues and under different physiological conditions such as viral infections. As intracellular parasites, viruses are confronted to cellular RNA modifying enzymes and, as a consequence, viral RNA can be chemically modified at some stages of the replication cycle. This review focuses on the chemical modifications of viral RNA and the impact that these modifications have on viral gene expression and the output of infection. A special emphasis is given to m⁶A, which was recently shown to play important yet controversial roles in different steps of the HIV-1, HCV and ZIKV replication cycles.