Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis.
Despite the identification of Epstein-Barr virus (EBV) in tumors of Burkitt's lymphoma (BL) over 40 years ago, the exact contribution of EBV to BL is undefined. EBV encodes for multiple proteins in latent B cells that affect B cell survival and activation. One such protein, latent membrane protein 2A (LMP2A), protects B cells from numerous pro-apoptotic stimuli. Therefore, we tested whether LMP2A protects B cells from apoptosis induced by aberrant c-MYC expression that precedes and dominates BL. We crossed LMP2A-transgenic mice (LMP2A-Tg), in which all B cells express LMP2A, to a transgenic mouse that expresses a BL translocation of myc (lambda-MYC-Tg mice). LMP2A promotes proliferation and protects B cells from MYC-induced apoptosis in lambda-MYC-Tg mice. LMP2A also accelerates the development of lymphoma in LMP2A/lambda-MYC-Tg mice. Finally, LMP2A increases the expression of Bcl-X(L) in both pre-tumor B cells and tumor cells, suggesting a mechanism for LMP2A-mediated B cell survival in the presence of MYC. These results support a hypothesis that EBV LMP2A promotes tumor development by protecting pre-tumor B cells that would normally apoptose after the c-myc translocation.
Bultema
R
R
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Longnecker
R
R
Swanson-Mungerson
M
M
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D016259:Genes, myc; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*; D051020:bcl-X Protein / Q000032:analysis
C494812:Bcl2l1 protein, mouse; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D051020:bcl-X Protein