Clever tricks EBV employed to modulate innate immunity during latency and lytic infection

Abstract

Epstein-Barr virus, a human γ-herpesvirus, persists in humans for life without being cleared by their immune system. Both innate and adaptive immunity contribute to the control of viral infections. However, antiviral immunity initiates with innate immune responses, for which recognition of conserved viral patterns by pattern recognition receptors (PRRs) is essential. Upon triggering, PRRs induce signaling routes through activation of transcription factors IRF3/IRF7 and NFκB. Since EBV is able to establish and maintain latency, and to complete virion synthesis without being eliminated, EBV is likely to modulate PPR-induced innate immune signaling. Multiple EBV-encoded and cellular gene products are involved in modulating innate immunity during both latent and lytic phase of infection by targeting PRR-induced signaling. Remarkably, EBV gene products have dual roles during infection, as innate immune signaling pathways are both induced and inhibited. This review first discusses briefly the herpesviridae and EBV, then innate immunity in host cells, focusing on Toll-like receptors (TLRs), RIG-l-like receptors (RLRs), and cytoplasmic DNA sensors in particular. Furthermore, this review provides a detailed overview of EBV recognition by these PRRs, and EBV-encoded gene products involved in modulating PRR-induced immune signaling during both latent and lytic infection. In addition, I propose a model for EBV modulation in the course of innate immunity depending on the time of infection. Knowledge of EBV evasion strategies should broaden our understanding of EBV infection and may reveal potential candidates for future prevention of EBV-associated diseases, including malignancies.