Unveiling Host and EBV Gene Expression Dynamics Following E2F1 Knockdown in P3HR1 Cells

E2F1, a member of E2F family transcription factors, is involved in the transcriptional regulation of genes required for G1 to S phase transition of the cell cycle, DNA replication and DNA repair along with apoptosis in response to DNA damage signals. Studies suggest that several DNA viruses deregulate E2F1 functions to modulate their replications. Our previous global transcriptomic analyses (GSE235941, GSE237484) reveal that E2F1 expression is transcriptionally activated during EBV latent infection in naïve B-lymphocytes but suppressed during reactivation into lytic-cycle replication. We hypothesize that EBV controls E2F1 expression to regulate its latent to lytic switch. To gain insights into the E2F1 mediated global transcriptional network of both cell and viral gene expressions in response to EBV lytic cycle induction, we knocked-down E2F1 in EBV positive P3HR1 cells and subjected to RNA-Seq analyses with or without lytic cycle inducer. The primary goals of our work were to identify the key cell pathways and the differential expression patterns of EBV latent and lytic genes upon E2F1 depletion. Our findings support the hypothesis that EBV controls latent to lytic switch by critically monitoring E2F1 expression, providing clues for therapeutic intervention.