Table 2.
Summary of major anti-HBV ISGs.
| ISGs | Characterization | Antiviral function | Mechanism | Different stages of HBV infection |
|---|---|---|---|---|
| MX2 ( 101) | Myxovirus resistance (Mx) protein, an evolutionarily conserved dynein-like large GTPase | MX2 can inhibit HBV infection and proliferation by reducing cccDNA level and inhibiting HBV RNA transcription. | When pgRNA transcription is driven by HBV’s own promoter and enhancer from the add-on vector, MX2 reduces HBV DNA replication by downregulating all replication markers | Inhibits HBV cccDNA formation and RNA transcription |
| SAMD4A ( 35) | SAMD4A is reported to be a mammalian homolog of Drosophila Smaug and to regulate post-transcriptional processes. | SAMD4A and its homolog SAMD4B can reduce HBV replication | SAMD4A mediates viral degradation by binding to the SRE site in viral RNA. | Promotes HBV RNA degradation and inhibits HBV replication |
| IFI6 ( 102) | IFI6 belongs to the FAM14 family localized on chromosome 1P35 and is an ISG | The overexpression of IFI6 inhibits HBV replication and translation in hepatocytes | IFI6 reduces HBV transcription and translation by inhibiting the ENHII/Cp promoter activity | Inhibits HBV DNA replication and RNA transcription |
| TRIM14 ( 103) | The members of the TRIM family are known for their RING finger E3-ubiquitin ligase activity -including a RING domain, 1 or 2 b-box domains, and associated coiled-coil domains in the amino-terminal region | Type I IFN-stimulated gene TRIM14 controls HBV replication by targeting HBx | The TRIM14 SPRY domain interacts with the C-terminus of HBx, which may block the role of HBx in promoting HBV replication by inhibiting the formation of the SMC-HBX-DDB1 complex. | Inhibits HBV RNA transcription and HBV replication |
| TRIM25 ( 104) | IL-27-dependent induction of TRIM25 inhibits HBV replication | Il-27 signaling is required for TRIM25 induction by type I IFN, and the transcription factors STAT1 and STAT3 play a role in TRIM25 induction. | Inhibits HBeAg secretion and HBV DNA replication | |
| ISG20 ( 105) | ISG20 has antiviral function against a variety of RNA viruses and is a 3’-5’ exonuclide induced by type I and type II IFNs. | ISG20 can bind and degrade HBV transcription factors and inhibit HBV replication. | ISG20 inhibits the HBV activity by binding to EnhII/Cp and inhibits HBV transcription by binding to YTHDF2 and recognizing m6A modifications. | Inhibits HBV transcription |
| miR-122 ( 106) | MiR-122 is a mammalian liver-specific microRNA that is highly expressed in the liver, accounting for 70% of the total miRNA population in the liver. | MiR-122 significantly inhibited HBV expression and replication | MiRNA-122 was positively correlated with ADAR1 expression, and NT5C3 was identified as the miR-122 target. | Inhibits HBV DNA formation and RNA transcription |
| ADAR1 ( 107) | ADAR1 is an ISG that catalyzes covalent modification of RNA substrates and produces inosine through C-6 deamination of hydrolyzed adenosine. | ADAR1 inhibited MAVS expression and reduced HBV marker levels in vitro and in vivo. | ADAR1 represses MAVS expression through human antigen R (HuR)-induced post-transcriptional regulation | Inhibits HBV DNA replication, RNA transcription, protein expression, and viral antigen packaging levels. |
| IDO ( 108) | IDO is an IFN-γ-induced enzyme that catalyzes tryptophan degradation | IDO effectively reduced HBV DNA content in cells without affecting viral RNA stabilization. | IDO can inhibit viral genome replication and translation, and this antiviral effect is mediated by tryptophan deprivation. | Inhibits HBV DNA replication and protein translation |
| OAS ( 109) | OAS encoded by the OAS gene uses adenosine triphosphate to synthesize 2’,5’ -oligadenylate (2’, 5’AS) in a 2’ -specific nucleotide transfer reaction, which activates latent ribonucrenase, leads to viral RNA degradation and inhibits viral replication | OAS gene variants may play an important role in the response to IFN-α | Polymorphism of IFN-induced gene OAS is associated with response to IFN-α therapy in chronic HBV infection | Promotes HBV RNA degradation and inhibits HBV replication |