Anti-hepatitis B virus activity and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein in vitro and in vivo.

AIMS

To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein (rHSA-IFNalpha-2b) in vitro and in vivo.

METHODS

The inhibiting effects on HBV replication were examined in the HepG2 2.2.15 cell line and in ducks, and the expressions of signal transducers and transactivator 1 (STAT1), IFN-stimulated gene factor 3 (ISGF3) and 2',5'-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.

RESULTS

In vitro,at concentrations from 0.075 to 1.2 nmol/l, rHSA-IFNalpha-2b inhibited the releases of extracellular hepatitis B surface antigen, hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA- IFNalpha-2b also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFNalpha-2b reduced the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin and duck hepatitis B virus (DHBV) DNA in the sera of DHBV-infected ducks.

CONCLUSIONS

We provide the first evidence that rHSA-IFNalpha-2b significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and that the antiviral effect of rHSA-IFNalpha-2b in vivo is more potent than that of IFNalpha-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT signaling pathway and increasing the expression of OAS1.