EBV Triggers a Distinct Antiviral Response in HMC3 Cells.
Article
Overview
abstract
Epstein-Barr Virus (EBV) is a gamma herpesvirus found in >90% of the world population that is associated with primary central nervous system (CNS) malignancy development in immunocompromised people. To provide mechanistic links between EBV infection and CNS malignancies, we investigated the capacity for EBV particles to suppress anti-tumor immunity in human microglia through a cell line model. With this approach, we exposed HMC3 cells to EBV-derived glycoprotein 350 (GP350), UV-inactivated EBV (UVi-EBV), and lipoteichoic acid (LTA) for up to 72 hours. Acute impacts of EBV particles and glycoprotein on microglial physiology were characterized at various timepoints in this model through measures of cytokine production, mRNA expression, and endocytosis. We found that UVi-EBV exposure significantly suppressed microglial production of anti-tumor interferons (IFNs) and upregulated microglial expression of the proto-oncogenic immediate early genes FOS and EGR1. Notably, there was no impairment of microglial endocytic functions following UVi-EBV stimulation, suggesting a compartmentalized suppression on IFN signaling. Overall, these findings reveal that the EBV-mediated inhibition of microglial IFN production may contribute to CNS malignancies and emphasize the urgency of innovating therapeutic strategies which target EBV to restore microglial anti-tumoral immunity.
