Back to Search
Start Over
Functional interplay of Epstein-Barr virus oncoproteins in a mouse model of B cell lymphomagenesis
- Publisher :
- Proceedings of the National Academy of Sciences
-
Abstract
- Epstein-Barr virus (EBV) is a B cell transforming virus that causes B cell malignancies under conditions of immune suppression. EBV orchestrates B cell transformation through its latent membrane proteins (LMPs) and Epstein-Barr nuclear antigens (EBNAs). We here identify secondary mutations in mouse B cell lymphomas induced by LMP1, to predict and identify key functions of other EBV genes during transformation. We find aberrant activation of early B cell factor 1 (EBF1) to promote transformation of LMP1-expressing B cells by inhibiting their differentiation to plasma cells. EBV EBNA3A phenocopies EBF1 activities in LMP1-expressing B cells, promoting transformation while inhibiting differentiation. In cells expressing LMP1 together with LMP2A, EBNA3A only promotes lymphomagenesis when the EBNA2 target Myc is also overexpressed. Collectively, our data support a model where proproliferative activities of LMP1, LMP2A, and EBNA2 in combination with EBNA3A-mediated inhibition of terminal plasma cell differentiation critically control EBV-mediated B cell lymphomagenesis.
- Subjects :
- Epstein-Barr Virus Infections
Herpesvirus 4, Human
Lymphoma, B-Cell
Plasma Cells
Primary Cell Culture
plasma cell differentiation
Viral Matrix Proteins
Mice
Viral Proteins
hemic and lymphatic diseases
Cell Line, Tumor
otorhinolaryngologic diseases
Epstein-Barr virus
Animals
Humans
LMP1
Mice, Knockout
B cell lymphomagenesis
Cell Differentiation
EBNA
Fibroblasts
Cell Transformation, Viral
3. Good health
DNA-Binding Proteins
stomatognathic diseases
Disease Models, Animal
Epstein-Barr Virus Nuclear Antigens
Trans-Activators
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........db52f0dfdf646e31ee2761e95b67c953