Interferon-α response in chronic hepatitis B-transfected HepG2.2.15 cells is partially restored by lamivudine treatment

Table 1 Complete list of genes investigated in this study

Gene Name	Acc. No.	Gene Name	Acc. No.	Gene Name	Acc. No.
101F6	AA544950	IFI 16	M63838	Mdm2	Z12020
2-5 OAS	X02875	IFI 41	L22342	MEN1	U93237
2-5 OAS	D00068	IFI 44	D28915	Met	AA410591
5' nucleotidase	X55740	IFI 6-16	BC015603	Mig	X72755
60S Ribosomal protein L11	U43522	IFI27	X67325	MIP-1b/CCL4	NM_002984
72 kDa type IV collagenase	J03210	IFI4	X79448	MLK 2	X90846
9-27	J04164	IFIT 1	M24594	MMP-1	M13509
ADAM-10	AF009615	IFIT4	U72882	MxA	M33882
ADAM-17	U69611	IFIT4	AF083470	MxA	M33882
akt-1	NM_005163	IFITM2	X57351	MxB	M30818
akt-2	M77198	IFITM3	X57352	MxB	M30818
Alpha-1-antiproteinase	K01396	IFN omega 1	X58822	NCAM	M74387
Alpha-crystallin	U05569	IFN-AR1	J03171	NF-IL-6	X52560
ATF-2	X15875	IFN-AR2	L42243	NFkB	M58603
Auto Ag SS-A/Ro	NM_003141	IFN-g	M29383	NKC-4	M59807
bad	U66879	IFN-GR1	J03143	n-myc	Y00664
BAK1	X84213	IFN-GR2	U05875	p19	U40343
BAX	U19599	IFI 17	J04164	p48/ISGF3g	M87503
Bax	L22474	IFP 35	U72882	p53	M14694
bcl-2	M14745	IFP-53	X62570	p57Kip2	U22398
BRCA1	U14680	IFRG28	AJ251832	p70 S6 kinase	M60724
BST2	D28137	ikBa	M69043	PAI-1	M16006
BTG1	X61123	IL-1 α	M28983	PCBP	M80563
Calcyclin	J02763	IL-10	M57627	PDGF-alpha	X06374
Calretiulin	M84739	IL-10 R α	U00672	PDK1	Y15056
CASP	AJ006470	IL-10 R β	Z17227	PDK2	NM_002611
Caspase 7	U67319	IL-12R β	U64198	Phosph. Scram. 1	AF098642
Caspase 8	X98172	IL13RA	U81379	Phosph.glycerate kin.	V00572
Caspase-1	M87507	IL13RA 2	U70981	Pi3-kinase	NM_006219
Caspase-9	U60521	IL-15	U14407	PIAS x-beta	AF077954
Cat. o-methyltransferase	M58525	IL-15RA	U31628	pig7	AF010312
CBFA	NM_004349	IL-18	D49950	pim-1	M16750
CBP	U85962	IL-18 bprot	AB019504	PK R	AF072860
CCR1	L09230	IL2	U25676	PKR	U50648
CCR5	U54994	IL-2R α	K03122	plectin (PLEC1)	U53204
CD5	X04391	IL2RG	D11086	PLOD2	U84573
cdk inhibitor p27KIP1	U10909	IL6	X04602	PML-1	M79462
C-fox	NM_005252	IL-8	M28130	PPP3CA	L14778
CG12-1	AF070675	IL8RB	L19593	Pro. 4-hydroxyl.	M24486
C-jun	J04111	iNOS	L09210	Prot.-ATPase-like pr.	D89052
C-myc	L00058	Int-6	U62962	PTEN	U96180
C-myc	V00568	Integrin β 7	M62880	pyridoxal kinase	U89606
Collagen α1 (I)	Z74615	integrin-β-6	NM_000888	raf (c-raf-1)	X03484
Collagen α2 (I)	J03464	IP-10	X02530	RAP46/Bag-1	Z35491
Collagen, type XVI, alpha 1	M92642	IP-30	J03909	RbAp48	X74262
Complement compound C1r	J04080	IRF 1	X14454	Reticulocalbin	D42073
COX17	L77701	IRF 4	U52682	RGS2	NM_002923
Cpp32	NM_004346	IRF 5	U51127	RHO	NM_000539
CREB	NM_004379	IRF-1	L05072	RHO GDP-dis.inh. 2	L20688
CTRL-1	X71877	IRF-2	X15949	RING 10	NM_004159
CXCR4	AF005058	Irf-7	U73036	RING4	X57522
Cyclin D1	M64349	ISG15	AA406020	Smad1	U59423
Cyp19 (aromata)	M28420	ISG15	M13755	Smad2	AF027964
Cys-X-Cys,member 11	AF030514	ISG-56K	M24594	Smad4	U44378
DEAD box binding protein 1	AF077951	KIAA0129	D50919	Smad5	U73825
DEAD-box protein p72	U59321	KIAA0235	D87078	Smad7	AF015261
Destrin	S65738	KIAA0284	AB006622	SnoN	X15219
DP (β1)	M83664	LIPA	U04285	SOCS 3/ssi-3	AB004904
DR-α	J00194	LMP-2	X66401	SOCS 4/CIS 4	AB006968
E2F-1	U47677	L-selectin	M25280	SOCS1	N91935
egr-1	X52541	Mad 4	X03541	SOCS-1	NM_003745
Elastase 2	M34379	MAP2K1	NM_002755	SOCS2	AF020590
ERM	X76184	MAP2K1IP1	NM_021970	SOCS-3	NM_003955
F-actin capping protein	U56637	MAP2K2	L11285	Stannin	NM_003498
Farn. pyro. syn.	J05262	MAP2K3	NM_002756	STAT 6	U16031
FAS/Apo-1	M67454	MAP2K4	L36870	STAT1 (91kDa)	M97935
fas-ligand	U08137	MAP2K5	NM_002757	STAT1 (91kDa)	M97935
Fibronectin-1	X02761	MAP2K6	U39657	STAT2	M97934
FK506 binding protein 6	AF038847	MAP2K7	AF022805	STAT4	L78440
FKHRL1	AF041336	MAP3K1	AF042838	STAT5A	L41142
Folate receptor	X62753	MAP3K11	NM_002419	STAT5B	U47686
gadd45	M60974	MAP3K14	NM_003954	Succinyl CoA Ligase	AF058953
Galectin-1	J04456	MAP3K2	NM_006609	TAP1 (Ring4)	L21204
Gamma actin	X04098	MAP3K3	U78876	TFE3	X96717
Gamma2-adaptin (G2AD)	AF068706	MAP3K4	NM_005922	TGF-bR1	L11695
GAPDH	X01677	MAP3K5	NM_005923	TGF-bR2	D50683
GATA 3	X58072	MAP3K7	NM_003188	TGF-bR3	L07594
GBP-1	M55542	MAP4K1	NM_007181	TGIF	X89750
GBP-2	M55543	MAP4K3	NM_003618	TIMP-1	M59906
Granzyme B	M17016	MAPK10	NM_002753	TIMP-2	J05593
GSK3	NM_002093	MAPK11	NM_002751	TIMP-3	U14394
HCV-ass. p44	D28915	MAPK12	NM_002969	TIMP-4	U76456
HLA-A (MHCI Ag B27)	NM_002116	MAPK13	AF004709	TNF-alpha	X01394
HLA-E	X56841	MAPK14	NM_001315	TRAF6	U78798
Homo sapins STAT	M97936	MAPK3	X60188	Transferrin	M12530
Hou	U32849	MAPK6	NM_002748	Transthyretin	D00096
HPAST protein	AF001434	MAPK7	NM_002749	TRIP14	L40387
hsf1 (tcf5)	M64673	MAPK8	NM_002750	trk oncogene	X03541
hsp90 (CDw52)	X15183	MAPK8IP2	NM_012324	TTF-2	AF073771
Hypoxia-ind. Factor-1	U22431	MAPK9	U35003	UBE2L6	AA292074
ICAM-1	M24283	MAPKAPK2	NM_004759	VCAM -1	M30257
ICSB 1	M91196	MAPKAPK3	NM_004635	VEGF-C	U43142
IDO	M34455	MCP-1/CCL2	X14768	Virpirin (Cig5)	AF026941

Genes of interest were selected from the UniGene database. These genes comprise known ISGs and genes of intrinsic interest which might or might not be induced by IFNs in different cell systems. They include genes involved in cell proliferation, immune responses and the responses to a variety of cytokines. 5’ IMAGE clones with 0.5-0.8 kb length were chosen and obtained from RZPD, Berlin, Germany.

Table 2 Suppression of ISG induction in HepG2.2.15 cells, effect of lamivudine treatment

Gene	Acc. No.	HepG2	2.2.15	HepG2/lam	2.2.15/lam
I complete inhibition
MxA	M33882	5.9	0.6	4.0	0.8
cig5	AF026941	2.2	0.9	2.1	1.2
II partial inhibition
IFITM3	X57352	3.4	1.6	3.4	1.8
IFITM2	X57351	2.7	1.6	2.2	1.8
III reversible inhibition
IFI 6-16	BC015603	7.9	4.4	7.2	6.5
IFITM1	M24594	4.9	2.5	4.8	4.6
IV no inhibition
2-5OAS	D00068	3.8	4.0	4.4	5.8
MxB	M30818	1.4	2.0	1.4	1.9
Caspase 7	U67319	2.3	2.4	2.2	2.1
IFI 17	J04164	3.3	2.9	2.8	2.7
IFI 27	X67325	1.9	2.1	1.8	2.2
IFI T4	U72882	2.7	1.9	2.6	1.8
RING4	X57522	2.4	2.3	2.5	3.5

Cells were stimulated with 100 U/mL IFN-α for 6 h with or without pre-treatment with 2 μmol/L lamivudine for 10 d. Then, RNA was isolated and assayed by cDNA macroarray. Data are shown as fold induction compared to the untreated control. Lam: Lamivudine.