Molecular analysis of the Epstein-Barr virus LMP1 in Hodgkin lymphoma from Argentina and Brazil: Identification of a distinct LMP1 deleted variant

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21099-21099
Author(s):  
P. Chabay ◽  
R. Hassan ◽  
D. Guiretti ◽  
P. Valva ◽  
M. Barros ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Geographic Area ◽  
Latent Membrane Protein 1 ◽  
South American ◽  
Barr Virus ◽  
Molecular Identity ◽  
Molecular Variant ◽  
Epstein Barr ◽  
New Mutations

21099 Background: Epstein Barr virus (EBV), a human oncogenic virus, has two types, EBV1 and 2, and several polymorphic markers allow individual variants to be distinguished. Variations in EBV latent membrane protein 1 (LMP1) gene could define a more oncogenic strain or reflect geographic EBV origin. By sequence analysis of C-ter, N-ter and promoter (prom) regions, 4 distinct EBV groups (A to D) have been defined. Aim: To analyze LMP1 molecular variability of two different groups of Hodgkin`s lymphoma (HL) from the same geographic area. Methods: EBV association by EBERs in situ hibridization and LMP1 immunohistochemistry was analyzed in 27 HL from Argentina (Arg) and 36 HL from Brazil (Br). EBV type was assessed by EBNA PCR. C-ter LMP1 PCR was done in all cases. Sequencing of C-ter, N-ter and prom regions was done in 16 patients. Results: 21/27 (78%) Arg HL and 31/36 (86%) Br HL were EBV1, while 6/27 (22%) and 4/36 (11%) were EBV2, respectively (p= 0.29). Coinfection was observed in 1 (3%) Br HL. LMP1 deleted (del) variant was observed in 20/27 (74%) Arg HL and 20/36 (55%) Br HL (p= 0.18), as well as in non-neoplastic controls, 4/11 and 3/10 (36 and 30%) from Arg and Br respectively. Most LMP1 del displayed high number (5–7) of 33bp repeats (86% LMP1 del Br HL and 77% LMP1 del Arg HL) compared with LMP1 wt that exhibited low number (3–4) 33bp repeats (68% LMP1 wt Br HL and 100% LMP1 wt Arg HL). Analysis of LMP1 sequences showed that: LMP1 wt C-ter regions had unmutated N-ter and prom as B95.8, A and B groups (31%), except for a case showing new mutations. LMP1 del C-ter regions showed molecular identity with C group, but they showed new, undescribed mutations in prom and N-ter (63%). Conclusions: We found high frequency of LMP1 del variants in HL from Argentina and Brazil, which was associated with high number of 33bp repeats in C-ter region. This suggests a role for this variant in lymphomagenesis. A new molecular variant with characteristic promoter and N-ter mutations was identified in LMP1 del cases, which could be proposed as a regional South American variant. No significant financial relationships to disclose.

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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