Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.

Deacon, E. M.; Pallesen, Gorm; Niedobitek, Gerald; Crocker, J; Brooks, Lucy; Rickinson, Alan B.; Young, Lawrence S.

doi:10.1084/jem.177.2.339

Cited by 325 publications

(158 citation statements)

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“…29 However no mRNA coding for EBNA-5 has been detected in RS cells by in situ hybridization studies. 30 Another study found an interaction between EBV-encoded EBNA-1 protein, which is expressed in all EBV-infected cells, and p53 protein. 31 In our study we found no relation between the level of p53 protein expression and the presence of EBV infection.…”

Section: Discussionmentioning

confidence: 98%

TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein-Barr virus

Maggio

Stekelenburg

Berg³

et al. 2001

Int. J. Cancer

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Epstein-Barr virus (EBV) infection probably has a role in this transforming event, which renders RS precursors resistance to apoptosis, as clonal EBV genomes can be detected in RS cells of classical HL in 30 -50% of cases. 3,4 EBV-encoded LMP-1 protein, known to be expressed in RS cells, is known for its immortalizing activity. 1,4 -6 EBV encoded EBNA-1 protein is also thought to have transforming capacity. 7,8 Moreover EBV is involved in immune suppression. 9,10 The major subset of HL of the nodular sclerosis subtype among the Western population is, however, frequently EBV negative. The distinct epidemiology of these cases has led to various speculations about their pathogenesis, but no other viruses have been identified to date. However, other transforming events such I B␣ gene mutations resulting in over-expression of NF-B as possible explanation of the rescue of these cells from apoptosis have been demonstrated. 11,12 The frequent finding of immunohistochemically detectable p53 protein expression in the nuclei of RS cells 4,13,14 suggests a possible role for p53 protein in the rescue of RS precursors from apoptosis. Wild-type p53 protein has the ability to intervene in cell proliferation and is necessary to maintain the integrity of the DNA.An aberrant p53 protein with lack of transcriptional activity can result in the survival of genetically unstable cells susceptible to malignant transformation. 15 A mutation in the TP53 gene is often associated with detectable p53 protein expression, because it stabilizes the protein as a consequence of conformational change. Several studies have demonstrated that a TP53 gene mutation causes impairment of p53 protein-mediated trans-activation. For HL a few studies have reported the presence of TP53 gene mutations in RS cells in only a minority of cases. 14,16,17 The low percentages of TP53 gene mutations (Ͻ10%) detected could be the result of the paucity of RS cells in the specimens, which may lead to false-negative findings. In general, higher TP53 gene mutation percentages were reported in studies with enrichment for RS cells. 13,18 -20 One exception was reported in a recent study in which even with enrichment no mutations were found. 21 Because TP53 gene mutations and EBV both can play a role in the resistance of RS precursors to apoptosis, the question arises whether these 2 potentially transforming events exclude each other. Chen et al. 13 found TP53 gene mutations in 6 of 16 EBVnegative cases and no mutations in 7 EBV-positive cases. This finding suggests that in some of the EBV-negative cases a TP53 gene mutation may be fundamental for the inhibition of apoptosis.To gain more insight in the frequency of TP53 gene mutations in HL and to test the hypothesis of an inverse correlation between the presence of TP53 gene mutations and EBV, we analyzed 67 cases of HL-involved tissues. All HL-involved tissues were analyzed for the presence of immunohistochemically detectable p53 protein and the presence of EBV. We enriched 15 EBV-positive and 11 EBV-negative HL-involved ti...

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Section: Discussionmentioning

confidence: 98%

TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein-Barr virus

Maggio

Stekelenburg

Berg³

et al. 2001

Int. J. Cancer

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“…In latency type I, which is found in Burkitt's lymphoma [23], EBV nuclear antigen (EBNA)-1 and BamHI A rightward fragments (BARTs) are expressed in addition to EBERs (Table 1). In latency type II, characteristics of Hodgkin's lymphoma [24] and nasopharyngeal carcinoma [25], EBNA-1, latent membrane protein (LMP)-1, LMP-2, BARTs, and EBERs are expressed (Table 1). In latency type III, associated with lymphoproliferative disorders [26], all latency genes, including EBNA-2 and EBNA-3s, are expressed ( Table 1).…”

Section: Classification Of Ebv-associated Diseases By Ebv Latent Genesmentioning

confidence: 99%

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

137

142

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Because Epstein-Barr virus (EBV) is ubiquitous and persists latently in lymphocytes, simply detecting EBV is insufficient to diagnose EBV-associated diseases. Therefore, measuring the EBV load is necessary to diagnose EBVassociated diseases and to explore EBV pathogenesis. Due to the diverse biology of EBV, the significance of measuring EBV DNA and the optimal type of specimen differ among EBV-associated diseases. Recent advances in molecular technology have enabled the EBV genome to be quantitated rapidly and accurately. Real-time polymerase chain reaction (PCR) is a rapid and reliable method to quantify DNA and is widely used not only as a diagnostic tool, but also as a management tool for EBV-associated diseases. However, each laboratory currently measures EBV load with its own ''homebrew'' system, and there is no consensus on sample type, sample preparation protocol, or assay units. The EBV real-time PCR assay system must be standardised for large-scale studies and international comparisons.

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“…In latency II, as noted in EBV-associated Hodgkin's disease and nasopharyngeal carcinoma, the EBNA-1, LMP-1 and LMP-2 genes but not other EBNA genes are transcribed (Brooks et al, 1992;Deacon et al, 1993). In latency I, EBV-infected cells express only EBNA-1, which is essential for episomal replication.…”

mentioning

confidence: 99%

The latency pattern of Epstein–Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

Iwatsuki

Oyama

et al. 2001

Br J Cancer

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SummaryThe nasal type, extranodal natural killer or T(NK/T)-cell lymphoma is usually associated with latent Epstein-Barr virus (EBV) infection. In order to elucidate the EBV gene expression patterns in vivo, we examined eight patients with cutaneous EBV-related NK/T-cell lymphomas, including six patients with a NK-cell phenotype and two patients with a T-cell phenotype. The implication of EBV in the skin lesions was determined by the presence of EBV-DNA, EBV-encoded nuclear RNA (EBER) and a clonality of EBV-DNA fragments containing the terminal repeats. Transcripts of EBV-encoded genes were screened by reverse transcription-polymerase chain reaction (RT-PCR), and confirmed by Southern blot hybridization. The expression of EBV-related antigens was examined by immunostaining using paraffinembedded tissue sections and cell pellets of EBV-positive cell lines. Our study demonstrated that all samples from the patients contained EBV nuclear antigen (EBNA)-1 mRNA which was transcribed using the Q promoter, whereas both the Q promoter and another upstream promoter (Cp/Wp) were used in EBV-positive cell lines, B95.8, Raji and Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was detected in seven of eight patients and all cell lines, whereas EBNA-2 transcripts were found only in the cell lines. Immunostaining showed no LMP-1, EBNA-2 or ZEBRA antigens in the paraffin-embedded tissue sections, although they were positive in the cell line cells. Latent BHRF1 transcripts encoding bcl-2 homologue and BCRF1 transcripts encoding viral interleukin (vIL)-10 were detected in one and two of eight patients, respectively. A patient with NK-cell lymphoma expressing both transcripts died of rapid progression of the illness. Our results indicate that the restricted expression of the latency-associated EBV genes and the production of vIL-10 and bcl-2 homologue may favour tumour growth, evading the host immune surveillance.

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Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells.

Cited by 325 publications

References 53 publications

TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein-Barr virus

TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein-Barr virus

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

The latency pattern of Epstein–Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas

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