scholarly journals Carboxy Terminal Variants of Epstein‐Barr Virus–Encoded Latent Membrane Protein 1 during Long‐Term Human Immunodeficiency Virus Infection: Reliable Markers for Individual Strain Identification

1999 ◽  
Vol 179 (1) ◽  
pp. 240-244 ◽  
Author(s):  
Christoph Berger ◽  
Debbie van Baarle ◽  
Marie José Kersten ◽  
Michèl R. Klein ◽  
A. Samer Al‐Homsi ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Strain Identification ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Individual Strain ◽  
Epstein Barr ◽  
Carboxy Terminal

scholarly journals Epstein-Barr Virus Strains With Latent Membrane Protein-1 Deletions: Prevalence in the Italian Population and High Association With Human Immunodeficiency Virus–Related Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1723-1731 ◽  
Author(s):  
Riccardo Dolcetti ◽  
Paola Zancai ◽  
Valli De Re ◽  
Annunziata Gloghini ◽  
Beatrice Bigoni ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Full Length ◽  
Latent Membrane Protein 1 ◽  
Italian Population ◽  
Neoplastic Cells ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr

Six Epstein-Barr virus (EBV)-related lymphoproliferative disorders were investigated to verify whether the EBV strain harbored by neoplastic cells had the same EBNA-2 and latent membrane protein-1 (LMP-1) DNA sequences of the virus carried by normal lymphocytes of the same patients. Within each case, the analysis of neoplastic lymph nodes, reactive lymphadenopathies, and/or EBV+ spontaneous lymphoblastoid cell lines gave concordant results with respect to type-specific EBNA-2 region and LMP-1 gene. In particular, five cases showed the same deletion in the 3′ end of the LMP-1 gene in both normal and neoplastic cells. We also determined the prevalence of LMP-1 deletions in a large series of normal peripheral blood mononucleated cells (PBMCs) from Italian individuals. The analysis showed that 50% (9 of 18) of PBMCs from human immunodeficiency virus (HIV)-seronegative donors carried a 30-bp deletion in the C-terminal portion of the LMP-1 gene, whereas a nondeleted fragment was amplified in about 44% (8 of 18) of the cases. Only one sample (5.6%) showed the amplification of a full-length LMP-1 band together with a deleted fragment. Similarly, PBMCs from HIV-infected patients showed an almost equivalent prevalence of full-length (17 of 37, 46%) and deleted (16 of 37, 43.2%) LMP-1 fragments, whereas about 11% of samples (4 of 37) showed evidence of double infections. Of note, deletions in the LMP-1 gene were detected with similar prevalence values in EBV+ Hodgkin's disease (HD) (13 of 30, 43.3%) and non-Hodgkin's lymphoma (NHL) (2 of 5, 40%) cases from HIV-seronegative patients and in HIV-related, EBV+ NHLs (4 of 7, 57.1%). Conversely, a 30-bp LMP-1 deletion was found in 10 of 12 HIV-associated HD cases (83%), a prevalence significantly higher than that detected in HIV-unrelated HD (P = .01). These findings indicate that: (1) the same EBV strain carrying LMP-1 deletions is harbored by normal and neoplastic cells of patients with EBV+ disorders, ruling out that these mutations might result from immunoselection phenomena; (2) in the Italian population, the prevalence of LMP-1 deletion mutants is comparable to that of EBV strains with full-length LMP-1; (3) HIV-induced immunosuppression is not associated with an increased prevalence of LMP-1 deletions in PBMCs; and (4) HIV-related HD cases, but not those of HIV-seronegative Italian patients, are closely correlated with the presence of LMP-1 deletions, suggesting that infection with these strains may increase the risk of developing HD in the HIV setting.

scholarly journals Epstein-Barr Virus Strains With Latent Membrane Protein-1 Deletions: Prevalence in the Italian Population and High Association With Human Immunodeficiency Virus–Related Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1723-1731 ◽  
Author(s):  
Riccardo Dolcetti ◽  
Paola Zancai ◽  
Valli De Re ◽  
Annunziata Gloghini ◽  
Beatrice Bigoni ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Full Length ◽  
Latent Membrane Protein 1 ◽  
Italian Population ◽  
Neoplastic Cells ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Epstein Barr

Abstract Six Epstein-Barr virus (EBV)-related lymphoproliferative disorders were investigated to verify whether the EBV strain harbored by neoplastic cells had the same EBNA-2 and latent membrane protein-1 (LMP-1) DNA sequences of the virus carried by normal lymphocytes of the same patients. Within each case, the analysis of neoplastic lymph nodes, reactive lymphadenopathies, and/or EBV+ spontaneous lymphoblastoid cell lines gave concordant results with respect to type-specific EBNA-2 region and LMP-1 gene. In particular, five cases showed the same deletion in the 3′ end of the LMP-1 gene in both normal and neoplastic cells. We also determined the prevalence of LMP-1 deletions in a large series of normal peripheral blood mononucleated cells (PBMCs) from Italian individuals. The analysis showed that 50% (9 of 18) of PBMCs from human immunodeficiency virus (HIV)-seronegative donors carried a 30-bp deletion in the C-terminal portion of the LMP-1 gene, whereas a nondeleted fragment was amplified in about 44% (8 of 18) of the cases. Only one sample (5.6%) showed the amplification of a full-length LMP-1 band together with a deleted fragment. Similarly, PBMCs from HIV-infected patients showed an almost equivalent prevalence of full-length (17 of 37, 46%) and deleted (16 of 37, 43.2%) LMP-1 fragments, whereas about 11% of samples (4 of 37) showed evidence of double infections. Of note, deletions in the LMP-1 gene were detected with similar prevalence values in EBV+ Hodgkin's disease (HD) (13 of 30, 43.3%) and non-Hodgkin's lymphoma (NHL) (2 of 5, 40%) cases from HIV-seronegative patients and in HIV-related, EBV+ NHLs (4 of 7, 57.1%). Conversely, a 30-bp LMP-1 deletion was found in 10 of 12 HIV-associated HD cases (83%), a prevalence significantly higher than that detected in HIV-unrelated HD (P = .01). These findings indicate that: (1) the same EBV strain carrying LMP-1 deletions is harbored by normal and neoplastic cells of patients with EBV+ disorders, ruling out that these mutations might result from immunoselection phenomena; (2) in the Italian population, the prevalence of LMP-1 deletion mutants is comparable to that of EBV strains with full-length LMP-1; (3) HIV-induced immunosuppression is not associated with an increased prevalence of LMP-1 deletions in PBMCs; and (4) HIV-related HD cases, but not those of HIV-seronegative Italian patients, are closely correlated with the presence of LMP-1 deletions, suggesting that infection with these strains may increase the risk of developing HD in the HIV setting.

scholarly journals Sequence Variations of Epstein-Barr Virus-Encoded Small Noncoding RNA and Latent Membrane Protein 1 in Hematologic Tumors in Northern China

Intervirology ◽  
2021 ◽  
Vol 64 (2) ◽  
pp. 69-80
Author(s):  
Hai-Yu Wang ◽  
Lingling Sun ◽  
Ping Li ◽  
Wen Liu ◽  
Zhong-Guang Zhang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Nested Pcr ◽  
Noncoding Rna ◽  
Epstein Barr Virus ◽  
Northern China ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Small Noncoding Rna ◽  
Barr Virus ◽  
Epstein Barr

<b><i>Objective:</i></b> To investigate the relationship between hematologic tumors and Epstein-Barr virus (EBV)-encoded small noncoding RNA (EBER) variations as well as latent membrane protein 1 (LMP1) variations. <b><i>Methods:</i></b> Patients with leukemia and myelodysplastic syndrome (MDS) were selected as subjects. Genotypes 1/2 and genotypes F/f were analyzed using the nested PCR technology, while EBER and LMP1 subtypes were analyzed by the nested PCR and DNA sequencing. <b><i>Results:</i></b> Type 1 was more dominant than type 2, found in 59 out of 82 (72%) leukemia and in 31 out of 35 (88.6%) MDS, while type F was more prevalent than type f in leukemia (83/85, 97.6%) and MDS (29/31, 93.5%) samples. The distribution of EBV genotypes 1/2 was not significantly different among leukemia, MDS, and healthy donor groups, neither was that of EBV genotypes F/f. EB-6m prototype was the dominant subtype of EBER in leukemia and MDS (73.2% [30/41] and 83.3% [10/12], respectively). The frequency of EB-6m was lower than that of healthy people (96.7%, 89/92), and the difference was significant (<i>p</i> &#x3c; 0.05). China 1 subtype was the dominant subtype of LMP1 in leukemia and MDS (70% [28/40] and 90% [9/10], respectively), and there was no significant difference in the distribution of LMP1 subtypes among the 3 groups (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> The distribution of EBV 1/2, F/f, EBER, and LMP1 subtypes in leukemia and MDS was similar to that in the background population in Northern China, which means that these subtypes may be rather region-restricted but not associated with leukemia and MDS pathogenesis.

Epstein-Barr virus latent membrane protein 1 mRNA is expressed in a significant proportion of patients with chronic lymphocytic leukemia

Cancer ◽  
2010 ◽  
Vol 116 (4) ◽  
pp. 880-887 ◽  
Author(s):  
Jeffrey J. Tarrand ◽  
Michael J. Keating ◽  
Apostolia M. Tsimberidou ◽  
Susan O'Brien ◽  
Rocco P. LaSala ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Membrane Protein ◽  
Epstein Barr Virus ◽  
Significant Proportion ◽  
Latent Membrane Protein ◽  
Lymphocytic Leukemia ◽  
Latent Membrane Protein 1 ◽  
Barr Virus ◽  
Epstein Barr ◽  
Virus Latent Membrane Protein

scholarly journals Tumor Suppressor p53 Stimulates the Expression of Epstein-Barr Virus Latent Membrane Protein 1

2017 ◽  
Vol 91 (20) ◽  
Author(s):  
Qianli Wang ◽  
Amy Lingel ◽  
Vicki Geiser ◽  
Zachary Kwapnoski ◽  
Luwen Zhang
Keyword(s):  
Dna Damage ◽  
Tumor Suppressor ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Tumor Suppressor P53 ◽  
Viral Oncogene ◽  
Barr Virus ◽  
Lmp1 Expression ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) is associated with multiple human malignancies. EBV latent membrane protein 1 (LMP1) is required for the efficient transformation of primary B lymphocytes in vitro and possibly in vivo. The tumor suppressor p53 plays a seminal role in cancer development. In some EBV-associated cancers, p53 tends to be wild type and overly expressed; however, the effects of p53 on LMP1 expression is not clear. We find LMP1 expression to be associated with p53 expression in EBV-transformed cells under physiological and DNA damaging conditions. DNA damage stimulates LMP1 expression, and p53 is required for the stimulation. Ectopic p53 stimulates endogenous LMP1 expression. Moreover, endogenous LMP1 blocks DNA damage-mediated apoptosis. Regarding the mechanism of p53-mediated LMP1 expression, we find that interferon regulatory factor 5 (IRF5), a direct target of p53, is associated with both p53 and LMP1. IRF5 binds to and activates a LMP1 promoter reporter construct. Ectopic IRF5 increases the expression of LMP1, while knockdown of IRF5 leads to reduction of LMP1. Furthermore, LMP1 blocks IRF5-mediated apoptosis in EBV-infected cells. All of the data suggest that cellular p53 stimulates viral LMP1 expression, and IRF5 may be one of the factors for p53-mediated LMP1 stimulation. LMP1 may subsequently block DNA damage- and IRF5-mediated apoptosis for the benefits of EBV. The mutual regulation between p53 and LMP1 may play an important role in EBV infection and latency and its related cancers. IMPORTANCE The tumor suppressor p53 is a critical cellular protein in response to various stresses and dictates cells for various responses, including apoptosis. This work suggests that an Epstein-Bar virus (EBV) principal viral oncogene is activated by cellular p53. The viral oncogene blocks p53-mediated adverse effects during viral infection and transformation. Therefore, the induction of the viral oncogene by p53 provides a means for the virus to cope with infection and DNA damage-mediated cellular stresses. This seems to be the first report that p53 activates a viral oncogene; therefore, the discovery would be interesting to a broad readership from the fields of oncology to virology.

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