Table 1 Roles of EBV-encoded latent genes
Latent genes | Roles |
|---|---|
EBNA-1 | Sequence-specific DNA-binding protein to EBV element; sequence-nonspecific chromosome association protein; transactivator of viral latent genes and host genes; responsible for episome replication, segregation and persistence of viral genome; involved in p53 degradation and oncogenesis |
EBNA-LP | Transcriptional coactivator of EBNA-2-dependent viral and cellular gene transcription; primarily indirectly associates with host DNA sites located at or near the transcriptional start; associates with cellular transcriptional (co)factors and EBNA-2; dismisses repressor complex from promoter or enhancer sites; is essential for EBV-mediated B-cell transformation |
EBNA-2 | Together with EBNA-LP cooperatively activates viral and cellular gene transcription for transformation; primarily indirectly associates with host DNA sites located at the enhancer or intergenic region; associates with cellular transcriptional (co)factors and EBNA-LP; is critical for EBV-mediated B-cell transformation |
EBNA-3A | A coactivator of EBNA-2, EBNA-3A and EBNA-3C associations with RBPJ inhibit RBPJ recruitments to DNA; downregulate cMyc transcription and block EBNA-2 activation effects; and induce CDKN2 and chemokines. Induces G1 arrests, which is essential for EBV-mediated B-cell transformation |
EBNA-3B | A coactivator of EBNA-2; dispensable for B-cell transformation; viral tumor suppressor; and upregulates CXCL10. EBNA-3B-knockout induces DLBCL-like tumors |
EBNA-3C | Coactivates with EBNA-2 host CXCR4 and CXCL12 genes; induces CDKN2, chemokines and aurora kinase B; mediates RB degradation; attenuates H2AX expression and overcomes EBV-infection-mediated DNA damage response; promotes cell proliferation; induces G1 arrests; essential for EBV-mediated B-cell transformation |
LMP-1 | Mimics the constitutively active form of CD40, a major EBV-encoded oncogene; activates NF-κB, JNK and p38 pathways; is critical for EBV-mediated B-cell transformation, a major EBV-encoded oncogene; activates NF-κB, JNK and p38 pathways; and induces EMT of NPC and acquisition of CSC-like properties |
LMP-2A | Mimics constitutively active, antigen-independent BCR signaling through constitutive activation of the ERK/MAPK pathway224; blocks antigen-dependent BCR signaling; induces B-cell lymphoma in transgenic condition; is important but not essential for in vitro primary B-lymphocyte growth transformation; rescues the LMP-1-generated impairment in germinal center in the response to antigen in animals; confers resting B cells sensitive to NF-κB inhibition and apoptosis; suppresses differentiation and promotes epithelial cell spreading and motility in epithelial cells; and enriches cancer stem cell-like population |
EBER | Most abundant EBV-encoded noncoding RNAs; augments colony formation and induces growth; confers cells resistance to PKR-dependent apoptosis; induces cytokines and modulates innate immune response; binds to La, PKR, L22, PRR and RIG-I; and EBER-mediated RIG-I activation likely contributes to EBV oncogenesis. EBER blockades of PKR-mediated phosphorylation of eIF2α results in blockage of eIF2α-mediated inhibition of protein synthesis and resistance to IFNα-induced apoptosis |
miRNAs | Transcribed from BART and BHRF1; validated targets include Bim, BRUCE, CXCL11, DICER1, PUMA; has a role in sustaining latently infected cells. BHRF1 miRNA and BART miRNAs interfere with apoptosis. The miR-BART15-3p promoted apoptosis 331 |
