Table 1.

Viral Gene Expression in ENKTL.

Gene(s)	Primary Function	Major Findings (as it relates to gene expression in ENKTL)	Reference(s)
EBER	In B cells, some evidence indicates that EBER expression protects against apoptosis and contributes to proliferation.	Thought to function via TLR3 to amplify the inflammatory response in HLH, CAEBV, and IM; unknown in ENKTL.	Iwakiri et al. J Exp Med, 2009.
EBNA1	Ensure faithful transmission of the circularized EBV episome to daughter cells by facilitating its replication during cell division.	Partial silencing in EBV+ NK cell line reduced cell proliferation.	Ian et al. Cancer Biol Ther, 2008.
EBNA2	DNA binding protein, interacts with cellular RBPJk.	Absent by IHC in tumors.	Chiang et al. Int J Cancer, 1996.
EBNA3	Affect transcription of viral and cellular genes.	Absent.	Chiang et al. Int J Cancer, 1996.
LMP1	Classic oncogene in B-cell transformation; modulator of cell signaling; induces a number of antiapoptotic proteins includes BCL2; functions to constitutively activate the TNF receptor and functionally resembles CD40, providing growth and differentiation signals to B-cells.	Expression is seen in the vast majority of cell lines but this does not mirror in vivo situation. Microenvironmental factors and cytokines (e.g., IL2, IL10) may be influential in expression in tumors. By IHC, some ENKTL tumors are LMP1-.	Chiang et al. Int J Cancer, 1996.
LMP2	Facilitate immortalization and lytic cycle but are not essential for B-cell transformation; may drive proliferation and survival of B-cells in the absence of BCR signaling.	Expression typically absent by IHC, although LMP2 specific CD8+ T-cells recognize and kill cell lines and induce clinical responses in patients. Subsequently, a novel LMP2 transcript was identified, which may serve as the target.	Fox et al. Blood, 2010. Chiang. Int J Cancer, 1996.
BZLF	Immediate-early genes; expressed following lytic activation.	Negative ZEBRA IHC in tumors.	Chiang et al. Int J Cancer, 1996.
BHRF1 miRNA cluster		No expression in cell lines. Detected in rare cells suggesting that lytic transcripts are most likely expressed by rare cells entering lytic cycle.	Chiang et al. Int J Cancer, 1996.
BART miRNA cluster		BART miRNAs are increased in cell lines. Mir-BART9 seems to influence expression of LMP1 and cell growth. mir-BART20-5p inhibits translation of T-bet in EBV-infected YT lymphoma cells of NK-cell origin.	Ramakrishnan et al. PLoS One, 2011. Lin et al. Am J Pathol, 2013.