Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2

Nat Med. 2002 Oct;8(10):1098-104. doi: 10.1038/nm758. Epub 2002 Sep 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / virology*
  • Cell Line
  • Down-Regulation*
  • Epstein-Barr Virus Infections / physiopathology
  • Epstein-Barr Virus Infections / virology*
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Epstein-Barr Virus Nuclear Antigens / metabolism*
  • Gene Expression Regulation, Viral
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Phenotype
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Viral Proteins
  • Virus Latency*


  • EBNA-2 protein, Human herpesvirus 4
  • Epstein-Barr Virus Nuclear Antigens
  • Proto-Oncogene Proteins c-myc
  • Viral Proteins