The viral lncRNA LMP2A-IT1 promotes Epstein-Barr virus lytic replication

The Epstein-Barr virus (EBV) employs lytic replication to facilitate viral propagation and pathogenesis; however, the regulatory mechanisms governing this process remain incompletely elucidated. Here, we identify LMP2A-IT1, a novel 276-nt RNA derived from the first intron of the LMP2A gene. This transcript directly interacts with the nuclear export factor exportin 5 (XPO5) and exhibits predominant cytoplasmic localization. Functionally, LMP2A-IT1 expression is markedly upregulated during EBV lytic reactivation and subsequently amplifies viral gene expression and DNA replication—a phenomenon further supported by the positive correlation between LMP2A-IT1 levels and EBV DNA copy numbers in human nasopharyngeal carcinoma tissues. Mechanistically, cytoplasmic LMP2A-IT1 likely activates inflammatory response, thereby upregulating the immediate-early transactivators BZLF1 and BRLF1 to initiate the EBV lytic cycle. Our study establishes LMP2A-IT1 as a novel EBV-encoded RNA and reveals its function as a key positive feedback regulator of EBV lytic replication. These findings provide new insights into EBV replication dynamics and underscore the functional significance of viral RNAs in EBV biology.