Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations.
Infection of human B cells with Epstein-Barr virus (EBV) was seen to result in activation-induced cytidine deaminase (AID) and polymerase-eta (pol-eta) gene expression. AID and pol-eta are cellular gene products that play central roles in the DNA-modifying processes involved in immunoglobulin gene class switch recombination and somatic hypermutation. Errors in these processes can result in oncogene mutation/translocation, thereby contributing to lymphomagenesis. It was seen that EBV infected, AID, and pol-eta expressing B cells accumulated mutations in cellular proto-oncogenes (BCL-6 and p53) that are known to be involved in the genesis of B cell lymphoma. The nature of the mutations seen in these oncogenes was consistent with the known activity of AID and pol-eta. These findings indicate that EBV induced AID and pol-eta expression, and that this was associated with oncogene mutation, providing a novel means by which EBV infection of B cells may contribute to lymphomagenesis.
Epeldegui
Marta
M
Department of Microbiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1740, USA.
Hung
Yee Ping
YP
McQuay
Amy
A
Ambinder
Richard F
RF
Martínez-Maza
Otoniel
O
D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D001483:Base Sequence; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral; D003564:Cytidine Deaminase / Q000235:genetics* / Q000276:immunology; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D020033:Protein Isoforms; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099270:Y-Family DNA Polymerases
D003564:Cytidine Deaminase; D004259:DNA-Directed DNA Polymerase; D020033:Protein Isoforms; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases