Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo

UMMS Affiliation

Department of Pediatrics; Program in Molecular Medicine

Publication Date


Document Type



Adolescent; Adult; B-Lymphocyte Subsets; Base Sequence; Burkitt Lymphoma; Cell Division; Cell Line; DNA, Viral; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; Gene Expression; Genes, Viral; Herpesvirus 4, Human; Humans; *Immunologic Memory; Models, Biological; Phenotype; Reverse Transcriptase Polymerase Chain Reaction


Immunology and Infectious Disease | Pediatrics


Epstein-Barr virus (EBV) is a herpesvirus that establishes a lifelong, persistent infection. It was first discovered in the tumor Burkitt's lymphoma (BL). Despite intensive study, the role of EBV in BL remains enigmatic. One striking feature of the tumor is the unique pattern of viral latent protein expression, which is restricted to EBV-encoded nuclear antigen (EBNA) 1. EBNA1 is required to maintain the viral genome but is not recognized by cytotoxic T cells. Consequently, it was proposed that this expression pattern was used by latently infected B cells in vivo. This would be the site of long-term, persistent infection by the virus and, by implication, the progenitor of BL. We now know that EBV persists in memory B cells in the peripheral blood and that BL is a tumor of memory cells. However, a normal B cell expressing EBNA1 alone has been elusive. Here we show that most infected cells in the blood express no detectable latent mRNA or proteins. The exception is that when infected cells divide they express EBNA1 only. This is the first detection of the BL viral phenotype in a normal, infected B cell in vivo. It suggests that BL may be a tumor of a latently infected memory B cell that is stuck proliferating because it is a tumor and, therefore, constitutively expressing only EBNA1.

DOI of Published Version



Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):239-44. Epub 2003 Dec 19. Link to article on publisher's site

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

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Link to Article in PubMed

PubMed ID