EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies.

摘要: The Epstein-Barr virus (EBV), which is a ubiquitous γ-herpesvirus, establishes latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over last 20 years, and account for approximately 1.5% all cancers worldwide 1.8% cancer deaths. However, potential involvement/contribution lytic proteins to pathophysiology not well understood. We previously demonstrated that EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate adaptive immune responses engaging Toll-Like Receptor 2 (TLR2), leads modulation downstream genes involved oncogenesis, chronic inflammation, effector T-cell function. Furthermore, examination serum samples from diffuse large B-cell lymphoma (DLBCL) lymphocytic leukemia patients revealed presence levels anti-dUTPase antibodies both cohorts compared controls with highest (3.67-fold increase) observed DLBCL female cases lowest (2.12-fold males. Using computer-generated algorithms, dUTPase amino acid sequence alignments, functional studies BLLF3 mutants, we identified putative motif TLR2 interaction. These findings suggest EBV-dUTPase: interaction molecular target could be used developing novel therapeutics (small molecules/vaccines).