Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice
Autor: | Youkyung Choi, Lucio Gama, Robert A. de Man, Andre Boonstra, Gertine W. van Oord, Martijn D. B. van de Garde, Suzan D. Pas, Thomas Vanwolleghem |
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Přispěvatelé: | Gastroenterology & Hepatology, Virology |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Hepatitis B virus Science viruses Alpha interferon Biology medicine.disease_cause Antiviral Agents Article Virus Polyethylene Glycols Mice 03 medical and health sciences Immune system SDG 3 - Good Health and Well-being Pegylated interferon Hepatitis E virus medicine Animals Humans Multidisciplinary Interferon-stimulated gene Interferon-alpha virus diseases Viral Load Virology Immunity Innate Recombinant Proteins Hepatitis E 3. Good health Chemokine CXCL10 Disease Models Animal 030104 developmental biology Humanized mouse Immunology Medicine Heterografts Viral load Engineering sciences. Technology Biomarkers medicine.drug |
Zdroj: | Scientific reports Scientific Reports, 7:8267. Nature Publishing Group Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
ISSN: | 2045-2322 |
Popis: | Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFNα doses in all mice and relapsed after a single pegIFNα injection in only half of treated animals. Rapid viral clearance by pegIFNα was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFNα treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFNα in immunocompromised humanized mice. |
Databáze: | OpenAIRE |
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