Figure 2.

Consequences of ribose 2′‐O‐methyl modifications on RNA virus gene expression. Methylation of the 2′‐O‐position on the ribose can occur on all nucleotides and may be deposited by both viral and cellular 2′‐O‐methyltransferases (2′‐O‐MTase). The 2′‐O‐methylation of the penultimate nucleotide of the 5′‐end of the viral RNA limits innate immune sensing, first by masking the recognition of the viral RNA by the cytosolic RNA sensors RIG‐I and Mda5 to prevent transcription of innate immune response genes, and second by preventing the interaction with IFIT proteins which downregulate translation. 2′‐O‐methylated nucleotides (Nm) within viral RNA also function to mask the viral RNA from cytosolic RNA sensors. Deposition of internal 2′‐O‐methyl groups on adenosines (Am) by the viral 2′‐O‐MTase inhibit the elongation of the viral RNA‐dependent RNA polymerase during replication