Epstein–Barr Virus and Innate Immunity: Friends or Foes?

Abstract

Epstein–Barr virus (EBV) successfully persists in the vast majority of adults but causes lymphoid and epithelial malignancies in a small fraction of latently infected individuals. Innate immunity is the first-line antiviral defense, which EBV has to evade in favor of its own replication and infection. EBV uses multiple strategies to perturb innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like, and AIM2-like receptors as well as cyclic GMP-AMP synthase. EBV also counteracts interferon production and signaling, including TBK1-IRF3 and JAK-STAT pathways. However, activation of innate immunity also triggers pro-inflammatory response and proteolytic cleavage of caspases, both of which exhibit proviral activity under some circumstances. Pathogenic inflammation also contributes to EBV oncogenesis. EBV activates NFκB signaling and induces pro-inflammatory cytokines. Through differential modulation of the proviral and antiviral roles of caspases and other host factors at different stages of infection, EBV usurps cellular programs for death and inflammation to its own benefits. The outcome of EBV infection is governed by a delicate interplay between innate immunity and EBV. A better understanding of this interplay will instruct prevention and intervention of EBV-associated cancers.

PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms

“…To further explore the mechanisms underlying PD-L1 overexpression in EBV (+) GC, we focused on the role of IFN-γ produced by tumor-infiltrating lymphocytes, including CD8 T cells, during virus infection 9 , 12 . Based on our recent finding that the IFN-γ gene signature correlates significantly with expression of CD274 mRNA in GC, we next attempted to investigate the effect of the IFN-γ signature on PD-L1/ CD274 expression in EBV (+) GC 10 .…”

“…EBV infection triggers innate antiviral immune responses in infected cells, which produce pro-inflammatory cytokines and type I IFNs 12 . During this response, interferon regulatory factor 3 (IRF3) plays a pivotal role.…”

“…IRF3 is a transcription factor that is usually activated in tumor cells through phosphorylation, dimerization, or nuclear translocation. IRF3 phosphorylation (pIRF3) in EBV-infected cells is triggered by EBV-encoded small RNAs (EBERs; e.g., EBER1 and EBER2) through the toll-like receptor (TLR) or RIG-I signaling pathways 12 , 13 . IRF3 also plays a role in adaptive T cell immune responses, as well as in innate immune responses 14 .…”

Stellenwert des maschinellen Blutbildes bei der Diagnose der infektiösen Mononukleose durch EBV

“…Für das EBV-Virus ist auch der direkte Befall von Monozyten beschrieben [17,18], welcher zu proinflammatorischen Reaktionen führt [19]. Der Einfluss der angeborenen Immunantwort bei der EBV-Infektion ist Gegenstand der aktuellen Forschung [20]. Das Gros der antiviralen Reaktion wird sicherlich jedoch von Zellen der adaptiven Immunantwort getragen, sodass die Rolle der Monozyten bei der akuten Infektion vernachlässigbar ist.…”

The role of soluble mediators in the clinical course of EBV infection and B cell homeostasis after kidney transplantation

“…EBV is a nearly ubiquitous γ-1 herpesvirus, infecting approximately 90% of the healthy population 3 – 5 . EBV primary infection commonly occurs in early childhood and targets B cells, establishing latency in the host memory B cells 3 , 6 – 8 . The use of immunosuppression can disrupt the delicate balance between immune system and latent virus control, causing a 50-fold increase of EBV-infected B cells in peripheral blood 9 , 10 .…”