Structural and functional outcomes of epitranscriptomic methylation of (+)RNA virus genomes – VIRAGE

The emergence of important viral human pathogens (eg., Dengue, Zika, SARS, MERS, Ebola viruses) cause substantial health and economic burden. These RNA viruses can rapidly evolve and escape antiviral responses by hiding their RNAs from detection by antiviral sensors. Their viral replication/transcription complex contains essential enzymes involved in RNA synthesis (polymerase) and epitranscriptomic RNA modifications (RNA methytransferases and sometimes exonucleases) responsible for luring the host cell. For selected viruses, here Flaviviruses and Coronaviruses, using our preliminary data and experimental systems developed in the 4 partner labs, we will address 1) the enzymology of RNA processing: synthesis, tagging, correcting, and evolving vRNA; 2) The innate immunity response elicited by RNA products of model viruses in infected cells; 3) the structural basis for the genome evolution machinery. Results aid antiviral drug-design, and connect the mechanistics of viral epitranscriptomic RNA modification to innate immunity.