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Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
Martijn D B van de Garde1, Suzan D Pas2, Gertine W van Oord1
1Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Scientific Reports
|August 17, 2017
Summary
Chronic Hepatitis E Virus (HEV) infections lack effective treatments. Pegylated interferon-alpha (pegIFNα) showed potent antiviral activity against HEV genotypes 1 and 3 in humanized mice, with limited immune response.
Area of Science:
- Hepatology and Virology
- Immunology and Infectious Diseases
Background:
- Limited antiviral options exist for chronic Hepatitis E Virus (HEV) infections.
- Immunological factors influencing HEV persistence are not well understood.
Purpose of the Study:
- To evaluate the antiviral efficacy of pegylated interferon-alpha (pegIFNα) against HEV.
- To investigate intrahepatic interferon-stimulated gene (ISG) responses during HEV infection and treatment.
Main Methods:
- Humanized mice infected with HEV genotypes 1 or 3 were treated with pegIFNα.
- Intrahepatic gene expression (qPCR, Nanostring) and serum CXCL10 levels were analyzed.
- Comparison with Hepatitis B Virus (HBV) infected animals was performed.
Main Results:
- PegIFNα rapidly cleared HEV genotypes 1 and 3 from liver and feces in all treated mice.
- HEV infections did not induce intrahepatic ISG responses in untreated humanized mice.
- PegIFNα treatment significantly increased ISG transcript levels and serum CXCL10 in HEV-infected mice.
Conclusions:
- Hepatitis E Virus genotypes 1 and 3 do not trigger innate intrahepatic immune responses.
- HEV infections are highly sensitive to pegIFNα treatment in immunocompromised humanized mice.
- PegIFNα effectively suppresses HEV replication, highlighting its potential as an antiviral therapy.
