AUTHOR=Zhang Jingwei , Sommermann Thomas , Li Xun , Gieselmann Lutz , de la Rosa Kathrin , Stecklum Maria , Klein Florian , Kocks Christine , Rajewsky Klaus TITLE=LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1331730 DOI=10.3389/fimmu.2023.1331730 ISSN=1664-3224 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.