Arsenicals, the integrated stress response, and epstein–barr virus lytic gene expression

Jaeyeun Lee, Jennifer Stone, Prashant Desai, John G. Kosowicz, Jun O. Liu, Richard F. Ambinder

Research output: Contribution to journalArticlepeer-review


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 As2 O3 on viral lytic gene expression. As2 O3 has also been reported to activate the ISR pathway by its activation of the heme-regulated inhibitor (HRI). Our investigations show that As2 O3 treatment leads to eIF2α 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 As2 O3 effects on EBV gene expression are also mediated through other pathways.

Original languageEnglish (US)
Article number812
Issue number5
StatePublished - May 2021


  • Arsenic
  • Epstein–Barr virus
  • Integrated stress response

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology


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