Interferon alpha induces a stronger antiviral effect than interferon lambda in HBV/HDV infected humanized mice

• Published in: Virus research 2024-11, Vol.349, p.199451, Article 199451
• Main Authors: Duehren, Sarah, Uchida, Takuro, Tsuge, Masataka, Hiraga, Nobuhiko, Uprichard, Susan L., Etzion, Ohad, Glenn, Jeffrey, Koh, Christopher, Heller, Theo, Cotler, Scott J., Oka, Shiro, Chayama, Kazuaki, Dahari, Harel
• Format: Article
• Language: English
• Subjects: Animals; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Coinfection - drug therapy; Coinfection - virology; Disease Models, Animal; DNA, Viral - blood; HBsAg; HBV DNA; HDV RNA; Hepatitis B - drug therapy; Hepatitis B - immunology; Hepatitis B - virology; Hepatitis B virus - drug effects; Hepatitis B virus - immunology; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - virology; Hepatitis D - drug therapy; Hepatitis D - immunology; Hepatitis D - virology; Hepatitis D, Chronic - drug therapy; Hepatitis D, Chronic - virology; Hepatitis Delta Virus - drug effects; Human albumin; Humanized mice; Humans; Interferon alpha; Interferon lambda; Interferon-alpha - pharmacology; Interferon-alpha - therapeutic use; Interferons; Mice; RNA, Viral - blood; Short Communication; Viral Load - drug effects; Virus Replication - drug effects
• ISSN: 0168-1702; 1872-7492; 1872-7492
• DOI: 10.1016/j.virusres.2024.199451

•Humanized mice provide a platform for studying hepatitis viral infection and treatment.•Liver-humanized mice which lack an adaptive immune response were included.•HDV, HBV, and HBsAg kinetics during IFNλ and IFNα treatments were assessed.•IFNα was more effective than IFNλ in decreasing HBV, HDV, and HBsAg. Recent studies indicate that treatment of chronic hepatitis D virus (HDV) with either pegylated interferon (IFN)λ or pegylated IFNα monotherapy leads to a dramatic decline in HDV RNA. Herein, we investigated the innate antiviral efficacy of IFNλ and IFNα in humanized mice that lack an adaptive immune response. Humanized mice were either co-infected with hepatitis B virus (HBV) and HDV simultaneously, or HDV infection was performed subsequent to HBV infection (i.e., superinfected). After steady viral replication was achieved, mice received either IFNλ (n = 6) or IFNα (n = 7) for 12 (or 13) weeks. Pretreatment median levels of serum HBV DNA (8.8 [IQR:0.2] log IU/ml), HDV RNA (9.8 [0.5] log IU/ml), HBsAg (4.0 [0.4] log IU/ml) and human albumin, hAlb (6.9 [0.1] log ng/mL) were similar between mice treated with IFNα or IFNλ and between those coinfected versus superinfected. Compared to mice treated with IFNλ, mice treated with IFNα had a significantly greater decline in HBV, HDV, and HBsAg levels. In conclusion, IFNα induces stronger inhibition of HBV and HDV than IFNλ in humanized mice that lack an adaptive immune response. Further studies are needed to assess the respective role of the combined innate-and adaptive-immune systems in the treatment of HBV and HDV with IFNα and IFNλ.