Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo
Hochberg, Donna ; Middeldorp, Jaap M. ; Catalina, Michelle D. ; Sullivan, John L. ; Luzuriaga, Katherine ; Thorley-Lawson, David A.
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Student Authors
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UMass Chan Affiliations
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Keywords
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
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Embargo Expiration Date
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Abstract
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.
Source
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