Attenuation of IFN signaling due to M6A modification of the host epitranscriptome promotes EBV lytic reactivation

N6-methyladenosine (m6A) modification is one of the most abundant post-transcriptional modifications that plays an important role in many pathophysiological conditions including host-pathogen interactions. A number of viruses were previously shown to manipulate the cellular m6A machinery usurping its function to their benefit during the course of their life cycle. Previously, we reported that EBV reprograms the host m6A system to regulate the stability of the viral transcripts and drive viral-mediated tumorigenesis by hijacking the functions of methyltransferase METTL14. We now report that during lytic reactivation EBV targets the RNA methylation system of the host to attenuate the innate immune response by suppressing the interferon response to facilitate a successful lytic replication. Overall design: LCL and AKATA cells treated with or without TPA and BA were incubated for 30 h before being lysed and total mRNA was extracted. RNA immuno precipitation was done using either m6A specific antibodies or by IgG control. The immunoprecipitated RNAs were processed for RNA sequencing according to the Trueseq RNA processing lit protocol.