Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post-transplant lymphoproliferative disorder suggest different roles for Epstein Barr virus

Abstract

Epstein Barr virus (EBV) infection is commonly associated with human cancer and, in particular, with lymphoid malignancies. Although the precise role of the virus in the pathogenesis of different lymphomas is largely unknown, it is well recognized that the expression of viral latent proteins and miRNA can contribute to its pathogenetic role. In this study, we compared the gene and miRNA expression profile of two EBV-associated aggressive B non-Hodgkin lymphomas known to be characterized by differential expression of the viral latent proteins aiming to dissect the possible different contribution of such proteins and EBV-encoded miRNAs. By applying extensive bioinformatic inferring and an experimental model, we found that EBV+ Burkitt lymphoma presented with significant over-expression of EBV-encoded miRNAs that were likely to contribute to its global molecular profile. On the other hand, EBV+ post-transplant diffuse large B-cell lymphomas presented a significant enrichment in genes regulated by the viral latent proteins. Based on these different viral and cellular gene expression patterns, a clear distinction between EBV+ Burkitt lymphoma and post-transplant diffuse large B-cell lymphomas was made. In this regard, the different viral and cellular expression patterns seemed to depend on each other, at least partially, and the latency type most probably played a significant role in their regulation. In conclusion, our data indicate that EBV influence over B-cell malignant clones may act through different mechanisms of transcriptional regulation and suggest that potentially different pathogenetic mechanisms may depend upon the conditions of the interaction between EBV and the host that finally determine the latency pattern.

EBV infection determines the immune hallmarks of plasmablastic lymphoma

“…36 In parallel, EBV is known to influence the transcriptional landscape of different EBV-associated lymphoma subtypes regardless to the expression of viral latent proteins program. 5,[37][38][39][40] Our study shows that relative to control tissues, both EBV + and EBV − PBL share and overexpress 15 immune escape genes. However in agreement with Rooney et al, 36 EBV + PBL samples upregulate even further these immune escape genes than EBV − PBL tumors.…”

The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment

“…In BL, therefore, EBV is more likely to have a supportive rather than a driving role, possibly by countering the pro-senescence and pro-apoptotic effects of unopposed c-MYC signaling via expression of the late lytic gene BHRF1 and of the BHRF1 and BART miR clusters or through viral-induced epigenetic repression of Bim, a pro-apoptotic protein [94, 95]. …”

Rapid Etiologic Diagnosis of Herpes Virus Infections in Children

“…Exceptionally, primary infection with EBV in older children can cause acute infectious mononucleosis instead of establishment of latency (18). Moreover, the expression of latency-related proteins and miRNA has been considered to play a role in the pathogenesis of different lymphomas (19). Serological tests are used in clinics to diagnose EBV, but heterophile antibodies are non-specific and not produced in some patients (17).…”