Antiviral potential of interferon-omega on hepatitis B virus replication in human hepatoma cells

Abstract

Interferon-alpha (IFN-alpha) and other cytokines are able to interfere with hepatitis B virus (HBV) replication. However, a sustained antiviral effect is achieved only in 25% to 40% of the patients with chronic HBV infection and clearance of the virus rarely occurs, stressing the need for developing therapeutic alternatives. In this study the antiviral potential of a new recombinant interferon, IFN-omega was investigated. IFN-omega was assessed in comparison with IFN-alpha 2c, IFN-gamma, and TNF-alpha with respect to production of HBV proteins and DNA in HepG2.2.15 cells, a HBV-DNA transfected hepatoma cell line which produces infectious viral particles. Cells were seeded at different states of confluence (20%-90%) and treated with increasing concentrations of interferons (5 to 5,000 U/ml), TNF-alpha (5 to 500 ng/ml), or combinations of both for one to three days. IFN-omega reduced the production of HBsAg down to 59% of the untreated controls, which was comparable to the reduction obtained by treatment with IFN-alpha (60%), the standard interferon used for the treatment of chronic HBV infections. The strongest inhibition, however, was achieved by treatment with 500 ng/ml TNF-alpha (42%). Likewise, production of HBeAg and synthesis of HBV DNA were inhibited to similar degrees by the different interferons. In non-replicating high-density cultures only TNF-alpha was effective. IFN-omega is of similar antiviral potential as IFN-alpha in this in vitro experimental system.