A subpopulation of normal B cells latently infected with Epstein-Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1

Fu, Chen; Zou, Jie-Zhi; Renzo, Livia Di; Winberg, Gösta; Hu, Li–Fu; Klein, Eva; Klein, George; Ernberg, Ingemar

doi:10.1128/jvi.69.6.3752-3758.1995

Cited by 199 publications

(68 citation statements)

References 44 publications

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“…As a consequence, certain latent genes (EBNA-2, EBNA-3A, EBNA-3C, EBNA-LP and LMP-1) have been apportioned an essential role in B cell transformation (Cohen et al, 1989;Hammerschmidt and Sugden, 1989;Mannick et al, 1991;Kaye et al, 1993;Tomkinson et al, 1993). However, the patterns of viral latent gene expression in cell culture and in vivo are profoundly different (Qu and Rowe, 1992;Chen et al, 1995). Moreover, viral expression in tumours differs from in vitro-infected B cells.…”

Section: Introductionmentioning

confidence: 99%

Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice.

1996

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The Epstein‐Barr virus (EBV) nuclear antigen‐1 (EBNA‐1) is a pleiotropic protein which has been characterized extensively both biochemically and functionally. It is the only one of the identified latent protein‐encoding genes to be consistently expressed in viral‐associated endemic Burkitt's lymphoma cells. As such, it is the only candidate viral protein to possibly perform a maintenance function in the tumour pathology. Despite this, no oncogenic activity has been attributed to the protein in tissue culture assays. The experiments described here were initiated to explore the activity of the protein in B cells in vivo. EBNA‐1 transgenic mice were generated with transgene expression directed to the B cell compartment using the mouse Ig heavy chain intron enhancer. Transgene expression was demonstrated in the lymphoid tissues of mice of two independent lines. Transgenic positive mice of both lines succumb to B cell lymphoma. The B cell tumours are monoclonal, frequently of follicular centre cell origin and remarkably similar to those induced by transgenic c‐myc expression. These results demonstrate that EBNA‐1 is oncogenic in vivo and suggest that the gene product may play a direct role in the pathogenesis of Burkitt's lymphoma and possibly other EBV‐associated malignancies.

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Section: Introductionmentioning

confidence: 99%

Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice.

1996

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“…In recent years, the advent of RT-PCR methodology as a tool to analyze the expression of critical genes in minute amounts of cells has paved the way to investigate the infection strategy of Epstein-Barr virus in vivo in normal and neoplastic cells (Klein, 1994). Thus far, a few studies have addressed this question by examining the pattern of EBV-gene expression in infected cells on peripheralblood mononuclear cells of healthy individuals (Qu and Rowe, 1992;Tierney et al, 1995;Chen et al, 1995). All the above studies have concluded that long-term persistence of EBV infection in vivo appears associated with the expression of a very limited number of EBV genes, namely EBNA-1 and/or LMP-2A.…”

Section: Detection Of Ebv-gene Transcription In Peripheral-blood Monomentioning

confidence: 99%

“…It is likely that the lower sensitivity of the RT-PCR strategy employed for the detection of EBNA-1 expression has led to under-estimation of the number of positive cases. Chen et al (1995) examined EBV-latent-gene-transcription status in small, high-density peripheral-blood B lymphocytes from normal healthy individuals. In that study, gene transcription encompassing either the Y3 or the Q exon was never detected.…”

Section: Detection Of Ebv-gene Transcription In Peripheral-blood Monomentioning

confidence: 99%

“…Qu and Rowe (1992) reported on the expression of LMP-2A, while Tierney et al (1994) found expression of EBNA-1 and LMP-2A, as compared with the expression of EBNA-1, LMP-1 and -2A and BZLF-1, during acute infection. Finally, Chen et al (1995) described a population of resting B cells where expression of EBNA-1, LMP-2A and the usage of C promoter has been shown. The lack of homogeneity in the results from the above studies, however, has left this issue far from being settled.…”

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confidence: 99%

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Transcription of latent and replicative Epstein‐Barr‐virus genes in bone‐marrow and peripheral‐blood mononuclear cells of healthy donors

Gonnella

Angeloni

Calogero

et al. 1997

Intl Journal of Cancer

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Reverse-transcriptase polymerase chain reaction has been used to analyze the expression of 2 latent genes (EBNA-1 and LMP-1) and one replicative gene (BZLF-1) of Epstein-Barr virus in mononuclear cells from bone marrow and peripheral blood of healthy donors. EBV-gene transcription was detected in 8 out of 15 bone-marrow samples. Among these, 5 allowed the detection of latency-associated transcripts in the absence of BZLF-1 expression. Only one sample showed positivity for expression of both latent and lytic genes. In 2 cases, BZLF-1 was the only transcript detected. In peripheral blood, 4 out of 7 samples showed evidence of EBNA-1 transcription; LMP-1 was expressed in 5 samples, and in 2 cases concomitant expression of EBNA-1 and BZLF-1 was detected. These results provide a direct demonstration by RT-PCR of EBV-gene transcription in bone-marrow-resident viral infected cells and suggest, in contrast to previous studies on peripheral blood, that LMP-1 and BZLF-1 are frequently transcribed also in absence of EBV-related disease. The heterogeneous viral gene expression found makes it difficult to define a pattern of viral latency in vivo which coincides with that described for lymphoblastoid or Burkitt's-lymphoma cell lines at different stages of differentiation.

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“…Tierney et al [2000a] reported that Wp was hypermethylated and that Cp was completely unmethylated in most patients with infectious mononucleosis. Promoter usage in healthy carriers is controversial [Tierney et al, 1994;Chen et al, 1995]. Paulson and Speck [1999] reported that Wp was hypermethylated but that Cp was only methylated sparsely to moderately in healthy carriers.…”

Section: Introductionmentioning

confidence: 99%

Latency pattern of Epstein‐Barr virus and methylation status in Epstein‐Barr virus‐associated hemophagocytic syndrome

Yoshioka

Kikuta

Ishiguro

et al. 2003

Journal of Medical Virology

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Expression of different panels of latent gene transcripts is controlled by usage of three distinct Epstein-Barr virus (EBV) nuclear antigen (EBNA) promoters (Wp, Cp, and Qp). EBV-associated hemophagocytic syndrome, which is often a fatal disease and generally occurs after primary EBV infection, is characterized by monoclonal or oligoclonal proliferation of EBV-infected T cells. The latency pattern and EBNA promoter (Wp, Cp, and Qp) usage in EBV-infected cells from three patients with EBV-associated hemophagocytic syndrome were examined by reverse transcription-polymerase chain reaction (PCR). Three samples from the patients expressed EBER, EBNA1, EBNA2, latent membrane protein (LMP)1, and LMP2A transcripts. The transcripts of EBNA1 were initiated from not only Wp/Cp but also Qp. Lytic cycle Fp-initiated EBNA1 and EBV lytic gene BZLF1 transcripts were not detected. The methylation statuses of three EBNA promoters in three patients with EBV-associated hemophagocytic syndrome and in two patients with infectious mononucleosis were also analyzed using bisulfite PCR analysis. Wp was hypermethylated, and Qp was unmethylated in both diseases. Cp was highly methylated in EBV-associated hemophagocytic syndrome, however, whereas Cp was almost unmethylated in infectious mononucleosis. These results suggest that there may be distinct EBV-infected cell populations in EBV-associated hemophagocytic syndrome, which exhibit different patterns of EBV latent gene expression. The methylation status in Cp and phenotype of EBV-infected cells may be critical differences in EBV-associated hemophagocytic syndrome and infectious mononucleosis.

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A subpopulation of normal B cells latently infected with Epstein-Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1

Cited by 199 publications

References 44 publications

Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice.

Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice.

Transcription of latent and replicative Epstein‐Barr‐virus genes in bone‐marrow and peripheral‐blood mononuclear cells of healthy donors

Latency pattern of Epstein‐Barr virus and methylation status in Epstein‐Barr virus‐associated hemophagocytic syndrome

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