Anti-Hepatitis B Virus Activity and Mechanisms of Recombinant Human Serum Albumin-Interferon-α-2b Fusion Protein in vitro and in vivo

Abstract

Aims:To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of recombinant human serum albumin-interferon-α-2b fusion protein (rHSA-IFNα-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-IFNα-2b inhibited the releases of extracellular hepatitis B surface antigen, hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA- IFNα-2b also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFNα-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-IFNα-2b significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and that the antiviral effect of rHSA-IFNα-2b in vivo is more potent than that of IFNα-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT signaling pathway and increasing the expression of OAS1.

Administration of recombinant IFN1 protects zebrafish (Danio rerio) from ISKNV infection

“…During acute infection with some viruses, such as hepatitis C virus (HCV) [16], hepatitis B virus (HBV) [17], foot-and-mouth disease virus [18], chicken infectious bronchitis virus (IBV) [19] and chicken infectious bursal disease virus (IBDV) [20], administration of recombinant interferon contributes to prevention of viral infection and progressive organs damage. Interferon protects hosts from clinical illness by delaying onset of diseases and decreasing severity of illness.…”

Changes in peripheral blood natural killer T cells in hepatitis B e antigen-positive chronic hepatitis B patients and efficacy prediction after pegylated interferon therapy

“…The anti-HBV roles of NKT cells are mainly expressed in 2 aspects (Li et al, 2011), including through its secreted cytokines and by activating other lymphocytes. The interferon can be expressed as the viral marker (antigen), thus making recognition by the immune system easier; however, interferon may also directly promote the activities of NK cells, macrophages, and T cells, enhancing their killing functions (Bingfa et al, 2009;Senturk et al, 2011). NKT cells secrete IFN-g, which may synergize and enhance antiviral activities.…”

IFN-CSP Inhibiting Hepatitis B Virus in HepG2.2.15 Cells Involves JAK-STAT Signal Pathway

“…To investigate the molecular mechanism of the anti-HBV effect of IFN-CSP, confluent HepG2.2.15 cells were pretreated for 1 h with 10 μ M of AG 490, a JAK inhibitor, and subsequently stimulated cells with either IFN-CSP or IFN α 2b for 3 days [ 17 ]. The supernatants were harvested for HBV antigens and HBV-DNA assays.…”