The inhibition of IRE1alpha/XBP1 axis prevents EBV-driven lymphomagenesis in NSG mice

Microbiol Spectr. 2023 Dec 12;11(6):e0263623. doi: 10.1128/spectrum.02636-23. Epub 2023 Oct 26.

Abstract

The novelty of this study lies in the fact that it shows that IRE1 alpha endoribonuclease inhibition by 4μ8C was able to counteract Epstein-Barr virus-driven lymphomagenesis in NOD SCID gamma mice and prevent B-cell immortalization in vitro, unveiling that this drug may be a promising therapeutic approach to reduce the risk of post-transplant lymphoproliferative disorders (PTLD) onset in immune-deficient patients. This hypothesis is further supported by the fact that 4μ8C impaired the survival of PTLD-like cells derived from mice, meaning that it could be helpful also in the case in which there is the possibility that these malignancies have begun to arise.

Keywords: EBV; IRE1alpha/XBP1s; NSG mice; lymphomagenesis.

MeSH terms

  • Animals
  • Endoribonucleases
  • Epstein-Barr Virus Infections*
  • Herpesvirus 4, Human
  • Lymphoproliferative Disorders* / therapy
  • Mice
  • Mice, SCID
  • Protein Serine-Threonine Kinases* / antagonists & inhibitors
  • Protein Serine-Threonine Kinases* / metabolism
  • X-Box Binding Protein 1 / antagonists & inhibitors
  • X-Box Binding Protein 1 / metabolism

Substances

  • Endoribonucleases
  • Protein Serine-Threonine Kinases
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Ern1 protein, mouse