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

Donna Hochberg, Jaap M Middeldorp, Michelle Catalina, John L Sullivan, Katherine Luzuriaga, David A Thorley-Lawson

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)239-44
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number1
DOIs
Publication statusPublished - 6 Jan 2004

Cite this

Hochberg, Donna ; Middeldorp, Jaap M ; Catalina, Michelle ; Sullivan, John L ; Luzuriaga, Katherine ; Thorley-Lawson, David A. / Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 1. pp. 239-44.
@article{5ab1e06b1a9a4948a62dbaa2ee069b1f,
title = "Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo",
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.",
keywords = "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, In Vitro Techniques, Models, Biological, Phenotype, Reverse Transcriptase Polymerase Chain Reaction, Journal Article, Research Support, U.S. Gov't, P.H.S.",
author = "Donna Hochberg and Middeldorp, {Jaap M} and Michelle Catalina and Sullivan, {John L} and Katherine Luzuriaga and Thorley-Lawson, {David A}",
year = "2004",
month = "1",
day = "6",
doi = "10.1073/pnas.2237267100",
language = "English",
volume = "101",
pages = "239--44",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "1",

}

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; Sullivan, John L; Luzuriaga, Katherine; Thorley-Lawson, David A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 1, 06.01.2004, p. 239-44.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo

AU - Hochberg, Donna

AU - Middeldorp, Jaap M

AU - Catalina, Michelle

AU - Sullivan, John L

AU - Luzuriaga, Katherine

AU - Thorley-Lawson, David A

PY - 2004/1/6

Y1 - 2004/1/6

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - B-Lymphocyte Subsets

KW - Base Sequence

KW - Burkitt Lymphoma

KW - Cell Division

KW - Cell Line

KW - DNA, Viral

KW - Epstein-Barr Virus Infections

KW - Epstein-Barr Virus Nuclear Antigens

KW - Gene Expression

KW - Genes, Viral

KW - Herpesvirus 4, Human

KW - Humans

KW - Immunologic Memory

KW - In Vitro Techniques

KW - Models, Biological

KW - Phenotype

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Journal Article

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1073/pnas.2237267100

DO - 10.1073/pnas.2237267100

M3 - Article

VL - 101

SP - 239

EP - 244

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

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

SN - 0027-8424

IS - 1

ER -