Guanylate-Binding Protein 1 (GBP1) Enhances IFN-α Mediated Antiviral Activity against Hepatitis B Virus Infection

摘要

Interferon-alpha (IFN-alpha) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-alpha antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFN alpha-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFN alpha-2b further increased the antiviral effect of IFN-alpha, while GBP1 silencing co-treatment with Peg-IFN alpha-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFN alpha-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFN alpha-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-alpha induced immune responses in response to HBV.