Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B

Table 2 Interferons with anti-hepatitis B virus properties

Types of Interferon		Effect on HBV				Remarks	Antiviral ISGs	Ref.
		cccDNA	rcDNA	HBs	HBe
I	IFN-α2a/PEG-IFN-α2a	↓	↓	↓	↓	Clinical anti-HBV agent	APOBEC3A1, APOBEC3F1, APOBEC3G1, STAT11, ISG201, TRIM38, MX1, etc.	[140-142]
	IFN-α2b/PEG-IFN-α2b	↓	↓	↓	↓	Clinical anti-HBV agent	IFITM1, IFITM3, TRIM14, RNASEL etc.	[143-145]
	IFN-α14	↓	-	↓	↓	Activates IFN-α and IFN-γ signalling	GBP4, GBP5	[146]
	IFN-β/PEG-IFN-β	↓	↓	↓	↓	-	MX1, CXCL10	[147]
	IFN-ω	-	↓	↓	↓	-	IRF1, IRF9, ISG15, OAS	[148-150]
II	IFN-γ	-	-	-	↓	-	APOBEC3G1, OAS, IDO	[151-153]
III	IFN-λ1a	-	↓	↓	↓	Increased HBe seroconversion	PKR, OAS	[154,155]
	IFN-λ2	↓	↓	-	↓	-	APOBEC3A1, APOBEC3B1, APOBEC3G1, MX1, OAS	[156]
	IFN-λ3	-	↓	↓	↓	Increased JAK/STAT signalling	APOBEC3G1, IRF91, IRF7, MX1, OAS, ISG15 etc.	[157-159]

↓: Reduced; -: Not determined.

¹Important for cccDNA elimination or silencing. HBV: Hepatitis B virus; rcDNA: Relaxed circular DNA; cccDNA: Covalently closed circular DNA; JAK: Activate janus kinase; STAT: Signal transducers and activators of transcription; ISGs: Interferon-stimulated genes; PEG: Pegylated form; IFN: Interferon.