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BACKGROUND:The Notch signaling pathway was originally identified as a pleiotropic cell-fate regulator through lateral inhibition.KSHV lytic switch protein RTA usurped this conserved pathway to activate lytic gene expression in a ligand-independent manner through functional interaction with RBP-Jk,the downstream transcription factor of Notch.Interestingly,the increased expression of both Notch ligands and receptors are observed both in KSHV latent infected cells and during KSHV lytic replication,indicating canonical Notch pathway may be important for KSHV life cycle.However,the function of classical Notch during KSHV reactivation has not been fully elucidated.