6533b85dfe1ef96bd12be7b1

RESEARCH PRODUCT

Overexpression of STAT-1 by adenoviral gene transfer does not inhibit hepatitis B virus replication.

subject

description

Objectives Interferons are known to inhibit the replication of hepatitis B viruses (HBV) in several animal models in vitro and in vivo as well in humans. The STAT-1 protein plays a central role in the biological activity of both type I and type II interferons. The lack of functional STAT-1 renders cells and organisms susceptible to bacterial and viral infectious agents. We analysed whether the overexpression of STAT-1 protein enhances the biological interferon response and whether it elicits antiviral acitivity against HBV in vitro. Methods To achieve an efficient STAT-1 overexpression in primary liver cells and hepatoma cells, we generated a recombinant, replication-deficient adenovirus expressing human STAT-1 (Adv-STAT-1). We analysed whether the overexpression of STAT-1 inhibits the replication of duck HBV and human HBV in vitro using Western blot analysis, the immunofluorescence of viral proteins and quantification of HBV-DNA copies, respectively. Results In the duck model of HBV infection the overexpression of STAT-1 neither inhibited an established infection nor prevented the establishment of duck HBV replication when administered simultanously with Adv-STAT-1. These observations were confirmed in an in-vitro model of human HBV infection using the human hepatoma cell line HepG2.2.15, which continously replicates HBV. Conclusion These data demonstrate that the over-expression of STAT-1 alone is not sufficient to strengthen the biological response of interferon as an antiviral agent.