LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells
Authors
- J. Zhang
- T. Sommermann
- X. Li
- L. Gieselmann
- K. de la Rosa
- M. Stecklum
- F. Klein
- C. Kocks
- K. Rajewsky
Journal
- Frontiers in Immunology
Citation
- Front Immunol 14: 1331730
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results identify a minimal set of EBV proteins sufficient for B cell transformation.