The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure

Martin, Baptiste; Coutard, Bruno; Guez, Théo; Paesen, Guido C; Canard, Bruno; Debart, Françoise; Vasseur, Jean-Jacques; Grimes, Jonathan M; Decroly, Etienne

This study reports three distinct methyltransferase activities carried out by the C-terminal region of SUDV L protein. Two of them are the traditional, cap-dependent N7 and 2'O methyltransferase activities that complete the synthesis of the viral cap structure, mimicking that on host mR-NAs, and enabling mRNA completion and translation. The third one, a cap-independent 2'O-A methyltransferase activity, was not described before, and may further promote virus survival, possibly by shielding the RNAs from intracellular sensors and restriction factors thus promoting immune evasion, or by regulating RNA encapsidation by the nucleoprotein. These methylations might thus be important during Ebola virus infection. Although it remains to be elucidated why this activity is specifically prevalent in Ebola viruses, it has clear potential as a potent antiviral target.