Identification of potential hot spots in the carboxy-terminal part of the Epstein-Barr virus (EBV) BNLF-1 gene in both malignant and benign EBV-associated diseases: high frequency of a 30-bp deletion in Malaysian and Danish peripheral T-cell lymphomas

Abstract

In this study, we have sequenced the C-terminal part of the Epstein- Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV-positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T-cell lymphomas (PTLs) and from tonsils of Danish infectious mononucleosis (IM). Our study showed that some of the 7 single-base mutations and the 30-bp deletion previously detected between codons of amino acid 322 and 366 in the BNLF-1 gene of the nasopharyngeal carcinoma cell line CAO were present in all Malaysian PTLs and in 60% of the Danish PTLs. In HD and the IM cases, the mutations were present in about 30%. The 30-bp deletion and the single base mutations occurred independently, and mutations were detectable in the majority of EBV type B-positive cases. These findings suggest that the 30-bp deletion and the 7 single-base mutations in the C-terminal part of the CAO-BNLF-1 gene do not characterize a new EBV type A substrain. Rather, some of the positions of single base mutations and the 30-bp deletion are hot spots that may have mutated independently through the evolution of EBV strains.

Epstein–Barr virus strains and variations: Geographic or disease‐specific variants?

“…Since the first published studies regarding the prevalence of EBV strains that EBV type 1 was described as the most predominant worldwide [Sample et al, 1990]. Literature shows that, despite the possible existence of coinfections, EBV type 1 is the predominant variant worldwide, especially in Caucasian and Asian populations while EBV type 2 is more frequently found in Africa [Apolloni and Sculley, 1994;Sandvej et al, 1994;Kim et al, 2002;Garc ıa-Cos ıo et al, 2008;Tiwawech et al, 2008;Chang et al, 2009;Bobek et al, 2010]. Nevertheless, there are very few studies in Africa.…”

Epstein–Barr viral infection in extranodal lymphoma of the head and neck: correlation with prognosis and response to treatment

“…A recent in vitro study has shown that del-LMP1 is associated with 30-70% prolongation of the half-life of the mutant protein. 25 Since LMP1 expression within human B lymphocytes induces DNA synthesis, abrogates apoptosis and plays an important role in the initiation and ⁄ or maintenance of the immortalized state, it is possible that the effects of LMP1 may be accentuated through loss of a genome segment required for its rapid turnover. Alternatively, cells with del-LMP1 may express an altered protein product with decreased immunogenecity for EBV-specific cytotoxic T cells.…”

Epstein‐Barr virus infection and its role in the expanding spectrum of human diseases

“…Additionally, peculiar deletions within the BamH1-N left-ward open reading frame-1 gene encoding the LMP-1 of EBV (so called 30-base pair (bp) deletion or 69 bp deletion) were evidenced in EBV genome-positive tumor cells with HD, NPC or peripheral T-cell lymphoma (17)(18)(19). Interestingly, LMP-1 may stimulate intercellular and intracellular signal transduction pathways, including nuclear factor-kappa B, a transcriptional factor controlling the expression of genes, involved in cell activation and growth control (20,21).…”

“…Interestingly, LMP-1 may stimulate intercellular and intracellular signal transduction pathways, including nuclear factor-kappa B, a transcriptional factor controlling the expression of genes, involved in cell activation and growth control (20,21). However, the fact that the 30-bp deletion and 6 of 7 single-base mutations was found as frequently in tonsils of acute IM (19). More recently, it was reported 30-bp deletion of LMP-1 had no prognostic significance of LPD which occurred in recipients with organ transplantation and was only reflective of the incidence of EBV strain in the regional population (22).…”

“…In the late 1980s, T cell lymphomas that occurred in patients with CAEBV were reported to contain EBV-DNA (2). Additionally, most of the aggressive peripheral T cell lymphoma predominantly affecting the nose, skin and gastrointestinal tract contained EBV-DNA in tumor tissues, in both Asian and European populations (19,37,50,51). Most of the lymphoma cells express the CD4, CD8 or natural killer phenotypes.…”