Table 1.

Four EBV-encoded absolute essential latent antigens and some of their major functions in naive B-cell transformation.

Latent antigens	Associated functions	Linked with other human cancers	Ref.
EBNA-1	Assists in EBV episome maintenance and replication, blocks interaction between HAUSP and p53 to facilitate p53 degradation	BL, HD, AAL and PTLD	[151]
EBNA-2	Transcriptional coactivator that upregulates expression of viral (LMP1) and cellular (c-myc) genes, interacts with RBP-Jκ and Notch signaling pathway	AAL and PTLD	[45,152]
EBNA-3C	Overrides both G1/S and G2/M cell cycle blockage, binds to RBP-Jκ and regulates viral gene transcription from Cp promoter, promotes LMP-1 expression, blocks p53-, E2F1- and Bim-mediated apoptotic cell deaths, enhances kinase activity of both cyclin D1/CDK6 and cyclin A/CDK2 complexes, induces degradation of p27KIP1 and pRb tumor-suppressor proteins, stabilizes c-Myc, cyclin D1 and MDM2, manipulates host chromatin remodeling machinery, interacts with and negatively modulates Nm23-H1-mediated metastatic suppression, and together with Nm23-H1, regulates Necdin-mediated transcriptional repression and antiangiogenic activities. Binds to MRS18-2 and directs it to the nucleus, where it functions as a pRb inhibitory factor	AAL and PTLD	[15,16,61,64,90,97,108]
LMP-1	Mimics CD40 ligand binding signal, stimulates bcl-2 and a20 expression to block apoptosis, acts as a constitutively active receptor for stimulating many cellular genes, regulates NF-κB, JAK/STAT, ERK MAPK, IRF and Wnt signaling pathways	HD, AAL and PTLD	[153]

AAL: AIDS-associated lymphoma; BL: Burkitt’s lymphoma; HD: Hodgkin’s disease; PTLD: Post-transplant lymphoproliferative disease.