Tumor suppressor p53 stimulates the expression of Epstein-Barr virus latent membrane protein 1

Qianli Wang, Amy Lingel, Vicki Geiser, Zachary Kwapnoski, Luwen Zhang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo. The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBVtransformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers.

Original languageEnglish (US)
Article numbere00312-17
JournalJournal of virology
Volume91
Issue number20
DOIs
StatePublished - Oct 1 2017

Keywords

  • EBV
  • Epstein-Barr virus
  • IRF5
  • LMP1
  • Latency
  • Transformation
  • p53

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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