Frontiers in Immunology (Dec 2023)

LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells

  • Jingwei Zhang,
  • Thomas Sommermann,
  • Xun Li,
  • Lutz Gieselmann,
  • Lutz Gieselmann,
  • Kathrin de la Rosa,
  • Kathrin de la Rosa,
  • Maria Stecklum,
  • Florian Klein,
  • Florian Klein,
  • Florian Klein,
  • Christine Kocks,
  • Klaus Rajewsky

DOI
https://doi.org/10.3389/fimmu.2023.1331730
Journal volume & issue
Vol. 14

Abstract

Read online

IntroductionEpstein-Barr virus (EBV) infection in humans is associated with a wide range of diseases including malignancies of different origins, most prominently B cells. Several EBV latent genes are thought to act together in B cell immortalization, but a minimal set of EBV genes sufficient for transformation remains to be identified.MethodsHere, we addressed this question by transducing human peripheral B cells from EBV-negative donors with retrovirus expressing the latent EBV genes encoding Latent Membrane Protein (LMP) 1 and 2A and Epstein-Barr Nuclear Antigen (EBNA) 2.ResultsLMP1 together with EBNA2, but not LMP1 alone or in combination with LMP2A was able to transform human primary B cells. LMP1/EBNA2-immortalized cell lines shared surface markers with EBV-transformed lymphoblastoid cell lines (LCLs). They showed sustained growth for more than 60 days, albeit at a lower growth rate than EBV-transformed LCLs. LMP1/EBNA2-immortalized cell lines generated tumors when transplanted subcutaneously into severely immunodeficient NOG mice. ConclusionOur results identify a minimal set of EBV proteins sufficient for B cell transformation.

Keywords