Table 1.

EBV immune evasion proteins and microRNAs.

EBV gene	Function /Phase /Location	Evasion mechanism	Ref.
LMP1	Latency II	Reducing TLR9 promoter activity; decreasing TLR9 mRNA and protein expression levels	[68]
		Reducing the phosphorylation of Tyk2 and STAT2; inhibiting IFN pathway activation	[78]
BGLF5	Lytic immune modulator	Depleting TLR9 mRNA and reducing its protein expression level	[69]
		Inducing host mRNA degradation; blocking the synthesis of MHC-I	[90]
BPLF1	Tegument	Removing ubiquitin tags from TRAF6; negatively regulating TLR signaling	[45]
		Mediating DUB-dependent deubiquitination of TBK1 and STING; inhibiting RIG-I-MAVS and cGAS-STING signaling	[72]
BHRF1	Lytic immune modulator	Inducing mitochondrial fission; causing MAVS protein degradation; blocking RLRs signaling	[70]
miR-BART6-3p	EBV-encoded microRNA	Targeting the 3’UTR of RIG-I mRNA; inhibiting the expression of IFN-β	[71]
BZLF1 (ZTA)	Lytic replication	Binding directly to IRF7; inhibiting IRF7 activation	[75]
		Upregulating SOCS3 expression; indirectly inhibiting IFN-α production	[76]
		Binding to CIITA; inhibiting MHC-II transcription	[93]
BRLF1 (RTA)	Lytic replication	Reducing the mRNA levels of IRF 3 and IRF7 and the activation of the IFN-β promoter; inhibiting the expression of IFN-β	[77]
LMP2	Latency II	Reducing the phosphorylation of Tyk2, STAT1 and JAK; inhibiting ISG transcription and the IFN production	[79]
LF2	Lytic immune modulator	Binding to IRF7 to block its dimerization; inhibiting IFN-α production	[80]
BGLF4	Late gene expression	Reducing the activity of IFN-β promoter; inhibiting IRF3 signaling	[81]
		Interfering with the interaction between NF-κB and UXT; inhibiting the activity of NF-κB	[82]
		Phosphorylating SAMHD1; decreasing the activity of dNTPase	[83]
miR-BART18-5p	EBV-encoded microRNA	Targeting MAP3K2; blocking viral replication	[86]
miR-BART4-5p	EBV-encoded microRNA	Downregulating proapoptotic protein BID activity; inhibiting target cells apoptosis	[87]
EBNA1	Latency I	Inhibiting ULBP1 and ULBP5; escaping NK cell recognition	[88]
BNLF2a	Lytic immune modulator	Inhibiting TAP function; preventing loading of antigenic peptides onto MHC-I	[91]
BILF1	Lytic immune modulator	Triggering endocytosis of MHC-I molecules and degradation	[92]
BZLF2	Entry glycoprotein	Binding to MHC-II complex; blocking the antigen recognition of CD4 + T cells	[94]

Abbreviation: EBV, Epstein‒Barr virus; LMP1: latent membrane protein 1; TLR: Toll-like receptor; Tyk: tyrosine kinase; STAT, transducer and activator of transcription; IFN, interferon; MHC-I/II: major histocompatibility complex class I/II molecules; TLR, Toll-like receptor; DUB, deubiquitinase; RIG-I: retinoic acid-inducible gene-I; RLRs: RIG-I -like receptors; MAVS, mitochondrial antiviral signaling; cGAS: cyclic GMP-AMP synthase; cGAMP, cyclic GMP-AMP; STING, stimulator of interferon genes; ER, endoplasmic reticulum; IRF, interferon regulatory factor; CIITA, class II transactivator; ISG, interferon-stimulated gene; IFN, interferon; SAMHD1: sterile alpha motif and HD domain 1; dNTPase: deoxynucleotide triphosphate hydrolase; EBNA: EBV nuclear antigen; ULBP, UL16-binding proteins; NK, natural killer; TAP, transporter associated with antigen processing.