Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2.
Epstein-Barr virus (EBV) is etiologically linked to endemic Burkitt lymphoma (BL), but its contribution to lymphomagenesis, versus that of the chromosomal translocation leading to c-myc gene deregulation, remains unclear. The virus's growth-transforming (Latency III) program of gene expression is extinguished in tumor cells, and only a single viral protein, the EBV nuclear antigen (EBNA)1, is expressed via the alternative Latency I program. It is not known if BL arises from a B-cell subset in which EBV naturally adopts a Latency I infection or if a clone with limited antigen expression has been selected from an EBV-transformed Latency III progenitor pool. Here we identify a subset of BL tumors in which the Latency III-associated EBNA promoter Wp is active and most EBNAs are expressed, but where a gene deletion has specifically abrogated the expression of EBNA2. This implies that BL can be selected from a Latency III progenitor and that the principal selection pressure is for downregulation of the c-Myc antagonist EBNA2.
Kelly
Gemma
G
Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, UK.
Bell
Andrew
A
Rickinson
Alan
A
D001402:B-Lymphocytes / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D015536:Down-Regulation; D020031:Epstein-Barr Virus Infections / Q000503:physiopathology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins; D017735:Virus Latency
C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D016271:Proto-Oncogene Proteins c-myc; D014764:Viral Proteins