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Cancers 2018, 10(5), 129; https://doi.org/10.3390/cancers10050129

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

1
Department of Cancer Biology and Genetics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
2
Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Received: 14 March 2018 / Revised: 20 April 2018 / Accepted: 25 April 2018 / Published: 1 May 2018
(This article belongs to the Special Issue Epstein–Barr Virus Associated Cancers)
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Abstract

The Epstein-Barr virus (EBV), which is a ubiquitous γ-herpesvirus, establishes a latent infection in more than 90% of the global adult population. EBV-associated malignancies have increased by 14.6% over the last 20 years, and account for approximately 1.5% of all cancers worldwide and 1.8% of all cancer deaths. However, the potential involvement/contribution of lytic proteins to the pathophysiology of EBV-associated cancers is not well understood. We have previously demonstrated that the EBV-deoxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate and adaptive immune responses by engaging the Toll-Like Receptor 2 (TLR2), which leads to the modulation of downstream genes involved in oncogenesis, chronic inflammation, and in effector T-cell function. Furthermore, examination of serum samples from diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia patients revealed the presence of increased levels of anti-dUTPase antibodies in both cohorts compared to controls with the highest levels (3.67-fold increase) observed in DLBCL female cases and the lowest (2.12-fold increase) in DLBCL males. Using computer-generated algorithms, dUTPase amino acid sequence alignments, and functional studies of BLLF3 mutants, we identified a putative amino acid motif involved with TLR2 interaction. These findings suggest that the EBV-dUTPase: TLR2 interaction is a potential molecular target that could be used for developing novel therapeutics (small molecules/vaccines). View Full-Text
Keywords: Epstein-Barr virus (EBV); deoxyuridine triphosphate nucleotidohydrolase (dUTPase); Toll-like receptor 2 (TLR2); diffuse large B cell lymphoma (DLBCL); chronic lymphocytic leukemia (CLL) Epstein-Barr virus (EBV); deoxyuridine triphosphate nucleotidohydrolase (dUTPase); Toll-like receptor 2 (TLR2); diffuse large B cell lymphoma (DLBCL); chronic lymphocytic leukemia (CLL)
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Williams, M.; Ariza, M.E. EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies. Cancers 2018, 10, 129.

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