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

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Chronic hepatitis D virus (HDV) infection is a significant global health concern.
• Pegylated interferon-alpha (IFNα) and pegylated interferon-lambda (IFNλ) are used in treating HDV.
• The innate antiviral efficacy of these interferons in the absence of adaptive immunity requires further investigation.

Purpose of the Study:

• To compare the innate antiviral efficacy of pegylated IFNλ and pegylated IFNα in humanized mice lacking adaptive immune responses.
• To evaluate the impact of simultaneous versus sequential infection with hepatitis B virus (HBV) and HDV on interferon treatment outcomes.
• To assess the reduction in HBV DNA, HDV RNA, and hepatitis B surface antigen (HBsAg) levels following interferon therapy.

Main Methods:

• Humanized mice, lacking adaptive immunity, were infected with HBV and HDV.
• Mice were either co-infected or superinfected with HDV after HBV infection.
• Following achievement of steady viral replication, mice received monotherapy with either pegylated IFNλ (n=6) or pegylated IFNα (n=7) for 12-13 weeks.

Main Results:

• Pretreatment viral loads (HBV DNA, HDV RNA, HBsAg) were comparable across all experimental groups.
• Mice treated with pegylated IFNα showed a significantly greater decline in HBV DNA, HDV RNA, and HBsAg compared to those treated with pegylated IFNλ.
• No significant differences in treatment efficacy were observed between co-infected and superinfected mice.

Conclusions:

• Pegylated IFNα exhibits stronger inhibition of HBV and HDV replication than pegylated IFNλ in a humanized mouse model devoid of adaptive immunity.
• These findings highlight the differential innate antiviral potency of IFNα and IFNλ against HBV/HDV.
• Further research is warranted to elucidate the combined roles of innate and adaptive immunity in interferon-based therapies for HBV and HDV.