EBV-dUTPase Modulates Host Immune Responses Potentially Altering the Tumor Microenvironment in EBV-associated...

Area of Science:

• Virology
• Immunology
• Oncology

Background:

• Long-term antiretroviral therapy (ART) improves immune function in HIV-1 patients but does not prevent non-Hodgkin's lymphoma or Hodgkin lymphoma.
• Epstein-Barr virus (EBV) is an independent risk factor for Diffuse Large B cell Lymphoma (DLBCL) and classical Hodgkin lymphoma, even in HIV-1 patients on ART.
• EBV-infected cells in malignancies typically express latency programs, but some express lytic replication genes, suggesting lytic products may drive lymphomagenesis.

Purpose of the Study:

• To investigate the role of EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) in lymphomagenesis.
• To determine if EBV-dUTPase is expressed in EBV-associated malignancies.
• To assess the impact of EBV-dUTPase on host immune responses and B-cell proliferation.

Main Methods:

• Expression of EBV-dUTPase was analyzed in nasopharyngeal carcinoma (NPC) tumors in a mouse model.
• IgG antibodies to EBV-dUTPase were measured in sera from patients with AIDS, DLBCL, NPC, and breast cancer (BC) using ELISA.
• The effect of EBV-dUTPase on T-cell function and EBV-immortalized B-cell proliferation was evaluated in an in vitro EBV infection model.

Main Results:

• EBV-dUTPase was expressed in NPC tumors in the mouse model.
• Elevated IgG antibodies to EBV-dUTPase were detected in subsets of patients with AIDS, DLBCL, and NPC compared to controls.
• In vitro, EBV-dUTPase was shown to inhibit T-cell function, facilitating the proliferation of EBV-immortalized B-cells.

Conclusions:

• EBV-dUTPase is expressed in EBV-associated malignancies.
• EBV-dUTPase may contribute to lymphomagenesis by modulating host immune responses.
• The protein promotes survival and proliferation of EBV-immortalized B-cells, potentially altering the tumor microenvironment.