Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo.
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.
Hochberg
Donna
D
Department of Pathology, Tufts University School of Medicine, Jaharis Building, 150 Harrison Avenue, Boston, MA 02111, USA.
Middeldorp
Jaap M
JM
Catalina
Michelle
M
Sullivan
John L
JL
Luzuriaga
Katherine
K
Thorley-Lawson
David A
DA
D000293:Adolescent; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002455:Cell Division; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D015870:Gene Expression; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008954:Models, Biological; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1