期刊
VIROLOGY
卷 416, 期 1-2, 页码 86-97出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.04.005
关键词
Epstein-Barr virus; Latent membrane protein 1; Promyelocytic leukemia protein nuclear bodies; Nasopharyngeal carcinoma; Idiopathic pulmonary fibrosis; Ganciclovir; Arsenic trioxide; Lytic reactivation; Zta
类别
资金
- NHLBI NIH HHS [R01 HL083901-04, R01 HL083901] Funding Source: Medline
Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies. (C) 2011 Elsevier Inc. All rights reserved.
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