Impact of Epstein-Barr Virus LMP2A on Toll-Like Receptor 9 (TLR9) expression and function 2257860

Abstract Introduction Toll-like receptor 9 (TLR9) in an important mechanism by which both innate and adaptive immune cells sense unmethylated DNA of bacteria and viruses. Epstein-Barr virus (EBV) is a double-stranded DNA enveloped virus that infects both epithelial cells and B cells. Since B cells express TLR9, we sought to determine if the latency protein, LMP2A, from EBV would impact TLR9 expression and/or function. Methods BJAB B cell lymphoma cells stably transfected with either vector, wildtype LMP2A or forms of LMP2A that harbor mutations in the N-terminal signaling tail were analyzed for TLR9 levels by flow cytometry. Additionally, these cells were stimulated with the TLR9 agonist, agatolimod (ODN2006), and the production of IL-6 was assessed by ELISA. Results The data indicate that LMP2A does not consistently alter TLR9 levels, but does enhance TLR9-induced cytokines, such as IL-6. The mechanism by which LMP2A confers this enhancement is currently under investigation. Conclusion TLR9 is an important innate sensing mechanism to identify the presence of pathogen’s DNA intracellularly. The ability of EBV to modulate signaling through these receptors may provide insight into mechanisms by which latency proteins regulate latency and B cell activation. Funding Source n/a Topic Categories Viral Immunology (VIR)