Table 1.
Mechanisms used by EBV to evade the host’s immune system.
| Molecule | Escape mechanism | References |
|---|---|---|
| EBNA1 | Prevents presentation of the major histocompatibility complex (MHC) class I-restricted EBNA1 epitope to cytotoxic T cells. | (78, 79) |
| EBNA2 | Creates an anti-inflammatory setting by triggering IL-37 and inducing IL-18 receptor expression in B cells. Moreover, it stimulates the induction of PD-L1 to help the virus evade the host’s immune response upon infecting primary B cells. | (80, 81) |
| LMP1 | Downregulates RIG-I signaling pathway by promoting RIG-I degradation dependent on proteasome, allowing the evasion of RIG-I mediated immune responses. | (82) |
| LMP2 | Encodes two transmembrane proteins: LMP2A and LMP2B. LMP2A can reduce MHC class II expression in lymphoblastoid cell lines through Class II transactivator (CIITA) downregulation. | (83) |
| vIL-10 | Impairs NK cell activity in destroying EBV-infected B cells and possessing various immunomodulatory activities by inhibiting cytokine expression. Also, it triggers less STAT3 phosphorylation, reduces anti-inflammatory gene expression, and inhibits M2 polarization in monocytes, contributing to autoimmune reactions in diseases like systemic lupus erythematosus (SLE) | (84, 85) |
| BNLF2a | Acts as an inhibitor of the Transporter associated with Antigen Processing (TAP), leading to reduced antigen presentation interfering with the recognition of CD8+ T cells and thus the detection of EBV-infected cells. | (84) |
| BPLF1 | Contributes to innate immune evasion through interference with Toll-Like receptor signaling, employing deubiquitination of TLR components. Furthermore, it is capable of leading to a decrease in type I IFN production by suppressing cGAS-STING and RIG-I-MAVS pathways. | (86, 87) |
| BGLF5 | Suppresses the expression of several immune components, including TLR9, TLR2, CD1d and HLA molecules, contributing to EBV immune evasion. | (88–90) |
| gp350 | Impairs the immune response by binding to CR2, preventing the CR2-C3d interaction that is important in the link between innate and adaptive immune responses. | (91, 92) |
| microRNAs | Helps viral escape from the immune response. miR-BART2, for example, targets the stress-induced immune ligand MICB, reducing its expression and thus resulting in escape recognition by natural killer cells. | (93–95) |