期刊
VIRUSES-BASEL
卷 13, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/v13050812
关键词
Epstein-Barr virus; integrated stress response; arsenic
类别
资金
- National Cancer Institute [P30CA06973]
Research found that As2O3 can increase EBV Zta gene expression while blocking late lytic gene expression and virion production. Additionally, the effects of As2O3 on EBV gene expression may be mediated by pathways other than the ISR signaling pathway.
Following our observation that clofoctol led to Epstein-Barr virus (EBV) lytic gene expression upon activation of the integrated stress response (ISR), we decided to investigate the impact of As2O3 on viral lytic gene expression. As2O3 has also been reported to activate the ISR pathway by its activation of the heme-regulated inhibitor (HRI). Our investigations show that As2O3 treatment leads to eIF2 alpha phosphorylation, upregulation of ATF4 and TRB3 expression, and an increase of EBV Zta gene expression in lymphoid tumor cell lines as well as in naturally infected epithelial cancer cell lines. However, late lytic gene expression and virion production were blocked after arsenic treatment. In comparison, a small molecule HRI activator also led to increased Zta expression but did not block late lytic gene expression, suggesting that As2O3 effects on EBV gene expression are also mediated through other pathways.
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