Reactivation of Epstein-Barr virus can be triggered by an Rta protein mutated at the nuclear localization signal

[[abstract]]Rta, an immediate-early protein of Epstein-Barr virus (EBV), is a transcriptional activator that induces lytic gene expression and triggers virus reactivation. Being located predominantly in, the nucleus, Rta can exert its transactivation function through either direct DNA binding of certain indirect mechanisms mediated by cellular signalling and other transcriptional factors. This study examined whether the subcellular localization of Rta was critical for the induction oil target genes. First (KRKK413)-K-410 was identified as a nuclear localization signal (NLS) of Ria. An Ria mutant with the NLS converted to (410)AAAA(413) showed cytoplasmic localization and failed to activate the promoter of BGLF5. Interestingly, ectopic expression of the Rta mutant still disrupted EBV latency in an epithelial cell line. Reporter gene assays revealed that the NLS-mutated Ria retained the ability to activate two lytic promoters, Zp and Rp, at a considerable level. Thus,, the cytoplasmic Rta mutant could induce expression of endogenous Zta and Ria. triggering reactivation of EBV