Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo
Middeldorp, Jaap M.
Catalina, Michelle D.
Sullivan, John L.
Thorley-Lawson, David A.
Document TypeJournal Article
Epstein-Barr Virus Infections
Epstein-Barr Virus Nuclear Antigens
Herpesvirus 4, Human
Reverse Transcriptase Polymerase Chain Reaction
Immunology and Infectious Disease
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AbstractEpstein-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.
SourceProc Natl Acad Sci U S A. 2004 Jan 6;101(1):239-44. Epub 2003 Dec 19. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43452
Related ResourcesLink to Article in PubMed