Epstein-Barr Virus and Lymphomagenesis

The role of EBV in lymphomagenesis is crucial. During EBV infection linear virus genome become circular and persists as an episome. Viral genome can express proteins of lytic or latent cycle. In latent cycle limited set of genes are expressed EBNA s, LMPs. Viral (onco)genes and RNA is under epigenetic control due to DNA methylation, acetylation and histone modifications. The switch from latent to lytic phase depends on activation of EBV immediate-early genes BZ LF1, BR LF1. Latent EBV infection bears immunogenic tendency shift from type 0 to type III and differ in protein expression – EBER , EBNA -1, 2, 3, LMP1,2, BARTs. Type III plays direct role in EBV oncogenesis (PTLD, HIV ass. lymphomas), high-level expression of all immunodominant latency proteins is detected. Type I, II plays cofactor´s role in EBV oncogenesis and is usually dected in immunocompetent individuals (BL, cHL, primary effusion DLBCL, AILT, ENK /T-cell lymphoma nasal type, Enteropathy-type T-cell lymphoma. In HL the virus genome express type II of latency virus proteins - EBNA 1, LMP1, LMP2. LMP1 is transforming protein, acts as protooncogene, as constitutively activated member of TNFR superfamily mimic CD40 and upregulates expression of CD23, CD40, BCL2 and NfkappaB. LMP2 blocks tyrosin kinase phosphorylation and prevents reactivation of EB V. EBNA -1 maintains EBV genome as episome. The deregulated expression of particular proteins in EBV transformed lymphoid cells could be important for EBV- driven lymphomagenesis and also for challenge in new therapeutic approach - infusion autologous EBV- specific T-lymphocytes, use of nucleoside analogue, proteasome inhibitor bortezomib or Bcl-2 inhibitor (HA14-4).

Acknowledgements: MSM 6198959205, IGA NT11103 and Leukemia and Lymphoma Research Fund.