Reactivation of Epstein-Barr virus can be triggered by an Rta protein mutated at the nuclear localization signal.
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 or 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 of target genes. First, 410KRKK413 was identified as a nuclear localization signal (NLS) of Rta. An Rta mutant with the NLS converted to 410AAAA413 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 Rta 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 Rta, triggering reactivation of EBV.
Hsu
Tsuey-Ying
TY
Department of Microbiology, College of Medicine, National Taiwan University, Room 722, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan.
Chang
Yao
Y
Department of Microbiology, College of Medicine, National Taiwan University, Room 722, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan.
Wang
Pei-Wen
PW
Department of Microbiology, College of Medicine, National Taiwan University, Room 722, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan.
Liu
Mei-Ying
MY
Center of General Education, National Taipei College of Nursing, Taipei, Taiwan.
Chen
Mei-Ru
MR
Department of Microbiology, College of Medicine, National Taiwan University, Room 722, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan.
Chen
Jen-Yang
JY
Extramural Research Affairs Department, National Health Research Institute, Taipei, Taiwan.|Department of Microbiology, College of Medicine, National Taiwan University, Room 722, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan.
Tsai
Ching-Hwa
CH
Department of Microbiology, College of Medicine, National Taiwan University, Room 722, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan.
D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism; D014775:Virus Activation
C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014764:Viral Proteins