Altogether, our results highlight the pivotal role of the L protein CTD in the control of viral RNA methylation, which is critical for Ebola virus replication and escape from the innate response in infected cells.IMPORTANCE Ebola virus infects human and non human primates causing severe infections that are often fatal. ...The Ebola virus large protein L , which is the central protein for viral RNA replication transcription, harbors a methyltransferase domain followed by a C terminal domain of unknown function. ...