Comprehensive Epstein-Barr Virus Transcriptome by RNA-Sequencing in Angioimmunoblastic T Cell Lymphoma (AITL) and Other Lymphomas

SIMPLE SUMMARY: Angioimmunoblastic 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. ABSTRACT: 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.