Journal Article

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

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

2023

Overview

Epstein-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. Here, 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. LMP1 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. Our results identify a minimal set of EBV proteins sufficient for B cell transformation.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: B cell lymphoma / Cell culture / Cell cycle / Cell immortalization / EBV latent genes / Epstein-Barr nuclear antigen 2 (EBNA2) / Epstein-Barr virus / Epstein-Barr virus (EBV) / Flow cytometry / Gene expression / Genetic transformation / Herpes viruses / Immortalization / Immunodeficiency / Immunology / Infections / Kinases / latent membrane protein 1 (LMP1) / LMP2A protein / Lymphoblastoid cell lines / Lymphocytes B / Lymphoma / lymphomagenesis / Malignancy / Metabolism / Mononucleosis / Protein expression / Proteins / Surface markers