Latent membrane protein 1 (LMP1) and LMP2A collaborate to promote Epstein-Barr virus-induced B cell lymphomas in a cord blood-humanized mouse model but are not essential

Shi Dong Ma, Ming Han Tsai, James C. Romero-Masters, Erik A. Ranheim, Shane M. Huebner, Jillian A. Bristol, Henri Jacques Delecluse, Shannon C. Kenney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Epstein-Barr virus (EBV) infection is associated with B cell lymphomas in humans. The ability of EBV to convert human B cells into long-lived lymphoblastoid cell lines (LCLs) in vitro requires the collaborative effects of EBNA2 (which hijacks Notch signaling), latent membrane protein 1 (LMP1) (which mimics CD40 signaling), and EBV-encoded nuclear antigen 3A (EBNA3A) and EBNA3C (which inhibit oncogene-induced senescence and apoptosis). However, we recently showed that an LMP1-deleted EBV mutant induces B cell lymphomas in a newly developed cord blood-humanized mouse model that allows EBV-infected B cells to interact with CD4 T cells (the major source of CD40 ligand). Here we examined whether the EBV LMP2A protein, which mimics constitutively active B cell receptor signaling, is required for EBV-induced lymphomas in this model. We find that the deletion of LMP2A delays the onset of EBV-induced lymphomas but does not affect the tumor phenotype or the number of tumors. The simultaneous deletion of both LMP1 and LMP2A results in fewer tumors and a further delay in tumor onset. Nevertheless, the LMP1/LMP2A double mutant induces lymphomas in approximately half of the infected animals. These results indicate that neither LMP1 nor LMP2A is absolutely essential for the ability of EBV to induce B cell lymphomas in the cord blood-humanized mouse model, although the simultaneous loss of both LMP1 and LMP2A decreases the proportion of animals developing tumors and increases the time to tumor onset. Thus, the expression of either LMP1 or LMP2A may be sufficient to promote early-onset EBV-induced tumors in this model.

Original languageEnglish
Article numbere01928-16
JournalJournal of Virology
Volume91
Issue number7
DOIs
StatePublished - 2017

Keywords

  • EBV
  • Epstein-Barr virus
  • Humanized mouse
  • LMP1
  • LMP2A
  • Lymphoma

Fingerprint

Dive into the research topics of 'Latent membrane protein 1 (LMP1) and LMP2A collaborate to promote Epstein-Barr virus-induced B cell lymphomas in a cord blood-humanized mouse model but are not essential'. Together they form a unique fingerprint.

Cite this