Control of hepatitis B virus replication by interferons and Toll-like receptor signaling pathways

Table 1 Summary of the anti-hepatitis B virus effects of interferons and interferon stimulated genes

	cccDNA minichromosome	Promoter and enhancer	Posttranscriptional control	Nucleocapsid formation	Others
IFNs	Modifying the composition of HBV minichromosome[27,29] Suppressing cccDNA transcription[27,29] accelerating cccDNA decay[29]	Suppressing HBV EnI and EnII activity[35-37]	Stimulating HBV RNA degradation[42,43]	Inhibiting nucleocapsid formation[48] Accelerating nucleocapsid degradation[49]
APOBEC	Blocking nucleocapsid maturation[65]	Suppressing HBV S promoter activity[57]			Editing HBV genome[70]
MxA			Inhibiting the nuclear export of HBV RNAs[77]	Blocking HBV nucleocapsid formation[78]
MyD88			Accelerating the decay of HBV pgRNA[83] Inhibiting the nuclear export of the HBV pre-S/S RNAs[83]
IDO			Inhibiting translation through tryptophan depletion[88]
TRIM22		Inhibiting HBV core promoter activity[92]
IFITs		Inhibiting HBV S promoter activity[96]	Inhibiting HBV replication at posttranscriptional steps[96]

HBV: Hepatitis B virus; IFN: Interferon; APOBEC: Apolipoprotein B mRNA editing enzyme: catalytic polypeptide; MyD88: Myeloid differentiation primary response protein 88; IDO: Indoleamine 2:3-dioxygenase; TRIM22: Tripartite motif-containing protein 22; IFITs: IFN-induced proteins with tetratricopeptide repeats 1 and 2.

Table 2 Control of hepatitis B virus replication by Toll-like receptor activation

	HBV transgenic mice[98]	Chimpazee[99]	Hepatoma cell line[100]	Nonparenchymal liver cells[104]	Macrophages[105]
TLR1/2	PGN and Pam3Cys, (-)		LTA , Pam2CSK4[102,103], Pam3CSK4[103], (+)	Pam3CSK4, (-)	Unpublished data, (+)
TLR3	Poly(I:C), (+)		Poly (I:C), (+)	Poly (I:C), (+)	Unpublished data, (+)
TLR4	LPS, (+)		LPS, (+)	LPS, (+)	Unpublished data, (+)
TLR5	Flagellin,(+)			Flagellin, (-)	Unpublished data, (+)
TLR7	R848, (+)		R848, (+)	Single-stranded RNA 40, (-)	Unpublished data, (+)
TLR9	CpG oligodeoxynucleotides, (+)	GS-9620, (+)	cpG DNA, (+)	CpG oligonucleotides, (-)	Unpublished data, (+)

The ligands of different Toll-like receptors (TLRs) used in different experiment systems were shown. Their effect on hepatitis B virus (HBV) replication was presented by ‘‘+’’ which means inhibitory effect or ‘‘-’’ which means no inhibitory effect.