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EBV Positive Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia Patients Exhibit Increased Anti-dUTPase Antibodies.
Williams, Marshall; Ariza, Maria Eugenia.
Afiliación
  • Williams M; Department of Cancer Biology and Genetics, The Ohio State University College of Medicine, Columbus, OH 43210, USA. williams.70@osu.edu.
  • Ariza ME; Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH 43210, USA. williams.70@osu.edu.
Cancers (Basel) ; 10(5)2018 May 01.
Article en En | MEDLINE | ID: mdl-29723986
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).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos