Epstein-Barr Virus (EBV) Is Mostly Latent and Clonal in Angioimmunoblastic T Cell Lymphoma (AITL)

SIMPLE SUMMARY: Angioimmunoblastic T cell lymphoma (AITL) is the most common peripheral T cell lymphoma encountered in Europe. It is a non-Hodgkin’s lymphoma with a poor prognosis. The Epstein-Barr virus (EBV) virus is detected in more than 90% of biopsies, especially in large B lymphocytes. To date, the role of EBV in this pathology is still debated. The aim of our study was to analyze whole viral genomes in AITL compared to other EBV-associated lymphomas. We observed that two viral strains were mainly found in AITL, one of which appeared to be associated with poor post-diagnosis survival. Furthermore, the virus was found to be clonal and latent in all cases of AITL; for one biopsy, the virus was both latent and most likely replicative, depending on the cells. On the whole, these results support a role for EBV in AITL. ABSTRACT: The Epstein-Barr virus (EBV) is associated with angioimmunoblastic T cell lymphoma (AITL), a peripheral T lymphoma of poor prognosis in at least 90% of cases. The role of EBV in this pathology is unknown. Using next-generation sequencing, we sequenced the entire EBV genome in biopsies from 18 patients with AITL, 16 patients with another EBV-associated lymphoma, and 2 controls. We chose an EBV target capture method, given the high specificity of this technique, followed by a second capture to increase sensitivity. We identified two main viral strains in AITL, one of them associated with the mutations BNRF1 S542N and BZLF1 A206S and with mutations in the EBNA-3 and LMP-2 genes. This strain was characterized in patients with short post-diagnosis survival. The main mutations found during AITL on the most mutated latency or tegument genes were identified and discussed. We showed that the virus was clonal in all the AITL samples, suggesting that it may be involved in this pathology. Additionally, EBV was latent in all the AITL samples; for one sample only, the virus was found to be latent and probably replicative, depending on the cells. These various elements support the role of EBV in AITL.