Anti-viral effects of interferon-λ3 on hepatitis B virus infection in cell culture.

Abstract

Interferon (IFN)-λ3 is known to have antiviral effects against various pathogens. Recently, it has been reported that the production of IFN-λ3 in colon cells after the administration of nucleotide analogs is expected to reduce hepatitisB surface antigen in chronic hepatitisB patients. Here, we aimed to prove the antiviral effects of IFN-λ3 on hepatitisB virus (HBV) by using an invitro HBV production and infection system. We used HepG2.2.15-derived HBV as an inoculum and the replication-competent molecular clone of HBV as a replication model. By administering IFN-λ3 to HepG2 cells transfected with the HBV molecular clone, the production of hepatitisB surface antigen and hepatitisB core-related antigen was reduced dose-dependently. IFN-λ3 treatment also reduced the number of HBV-positive cells and the synthesis of covalently closed circular DNA after infection of HepG2.2.15-derived HBV to sodium taurocholate cotransporting polypeptide-transduced HepG2 cells. The inhibitory effect on HBV infection by IFN-λ3 was confirmed by using a recombinant a HBV reporter virus system. To elucidate the underlying mechanisms of the anti-HBV effect of IFN-λ3, we assessed the transcription of HBV RNA and the production of core-associated HBV DNA in HBV molecular clone-transfected HepG2 cells, and found that both parameters were reduced by IFN-λ3. We observed that the administration of IFN-λ3 inhibits HBV infection and the production of HBV proteins at the HBV RNA transcription level. This finding provides novel insight into the treatment of chronic hepatitisB patients with the administration or induction of IFN-λ3.