Abstract
Simple SummaryAngioimmunoblastic T cell lymphoma (AITL) is probably the most common peripheral T-cell lymphoma. This pathology, although rare, is more common in Europe than in other regions. This lymphoma has a poor prognosis. AITL is very commonly associated with the Epstein-Barr virus (EBV) although the virus is not often found in neoplastic T cells but rather in adjacent B cells. Our objective was to study the transcriptome of EBV in AITLs comparatively to other EBV-associated lymphomas and to compare the results with those obtained for cell lines. We showed in AITLs a strong expression of Bam-HI A rightward transcripts (BARTs) more expressed than in the other lymphomas and especially than in cell lines. BARTs can participate in tumor development. We also showed a latency IIc in AITLs with the expression of BNLF2a and BCRF1 genes which may participate in the survival of infected cells. These results support the involvement of EBV in AITLs.The Epstein–Barr virus (EBV) is associated with angioimmunoblastic T cell lymphoma (AITL) in more than 80% of cases. Few studies have focused on this association and it is not clear now what role the virus plays in this pathology. We used next-generation sequencing (NGS) to study EBV transcriptome in 14 AITLs compared to 21 other lymphoma samples and 11 cell lines including 4 lymphoblastoid cell lines (LCLs). Viral transcripts were recovered using capture probes and sequencing was performed on Illumina. Bam-HI A rightward transcripts (BARTs) were the most latency transcripts expressed in AITLs, suggesting they may play a role in this pathology. Thus, BARTs, already described as highly expressed in carcinoma cells, are also very present in AITLs and other lymphomas. They were poorly expressed in cell lines other than LCLs. AITLs showed a latency IIc, with BNLF2a gene expression. For most AITLs, BCRF1, which encodes a homologous protein of human interleukin 10, vIL-10, was in addition expressed. This co-expression can contribute to immune escape and survival of infected cells. Considering these results, it can be assumed that EBV plays a pathogenic role in AITLs.
Highlights
The Epstein–Barr virus (EBV) is a widespread human gamma-herpesvirus of which two types can be distinguished, EBV type 1 (EBV-1) and EBV type 2 (EBV-2), according to geographic distribution, virulence, and differences in the latent genes (principally Epstein– Barr nuclear antigen-2 (EBNA-2), -3A, and -3C genes) [1]
In this study, we examined the EBV transcriptome in 14 angioimmunoblastic T cell lymphoma (AITL) biopsies compared to other EBV positive lymphomas and cell lines by RNA-seq, We demonstrated for AITLs a significant expression of Bam-HI A rightward transcripts (BARTs) superior to that observed for other lymphomas
We studied the EBV transcriptome in B95-8 line, initially obtained from a primary infection, in four Burkitt’s lymphoma (BL) lines (Jijoye, Namalwa, P3HR1, and Raji), in two NK/T lymphoma (NK/TL) lines (SNK6 and MEC04), characteristics of which are mentioned in Table 2 and in four lymphoblastoid cell lines (LCLs) that we established (CoAN, DPL, KREB2, and MLEB2)
Summary
The Epstein–Barr virus (EBV) is a widespread human gamma-herpesvirus of which two types can be distinguished, EBV type 1 (EBV-1) and EBV type 2 (EBV-2), according to geographic distribution, virulence, and differences in the latent genes (principally Epstein– Barr nuclear antigen-2 (EBNA-2), -3A, and -3C genes) [1]. The primary infection is followed by a lifelong latency defined by the absence of production of new infectious virions. In the event of infected cell activation, episodes of viral reactivation may occur, corresponding to a resumption of the lytic cycle with the production of infectious virus [3]. First resting B-cell EBV infection leads to expression of the Epstein–Barr nuclear antigen-2 (EBNA-2) and EBNA-Leader Protein (EBNA-LP) proteins as well as latent BHRF1, a bcl homolog protein, driven by the activated viral promoter Wp [4]. The upstream viral promoter Cp is activated by both expressed EBNAs and the cellular factor recombination signal binding protein for the immunoglobulin Kappa J region (RBP-Jκ), leading to the production of the six EBNA proteins, EBNA-1, EBNA-2, EBNA-3A, -3B, -3C, and EBNALP.
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