학술논문

LMP1 and EBNA2 constitute a minimal set of EBV genes for transformation of human B cells
Document Type
article
Source
Frontiers in Immunology, Vol 14 (2023)
Subject
B cell lymphoma
lymphomagenesis
Epstein-Barr virus (EBV)
EBV latent genes
Epstein-Barr nuclear antigen 2 (EBNA2)
latent membrane protein 1 (LMP1)
Immunologic diseases. Allergy
RC581-607
Language
English
ISSN
1664-3224
Abstract
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.