Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice

Martijn D.B. Van De Garde, Suzan D. Pas, Gertine W. Van Oord, Lucio Gama, Youkyung Choi, Robert A. De Man, Andre Boonstra, Thomas Vanwolleghem

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number8267
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Hepatitis Viruses
Virus Diseases
Hepatitis E virus
Interferon-alpha
Interferons
Therapeutics
Liver
Genotype
Antiviral Agents
Genes
Chronic Hepatitis
Infection
Serum
Innate Immunity
Hepatitis B virus
Feces
Hepatocytes
Gene Expression
Injections

ASJC Scopus subject areas

  • General

Cite this

Van De Garde, M. D. B., Pas, S. D., Van Oord, G. W., Gama, L., Choi, Y., De Man, R. A., ... Vanwolleghem, T. (2017). Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice. Scientific Reports, 7(1), [8267]. https://doi.org/10.1038/s41598-017-07434-y

Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice. / Van De Garde, Martijn D.B.; Pas, Suzan D.; Van Oord, Gertine W.; Gama, Lucio; Choi, Youkyung; De Man, Robert A.; Boonstra, Andre; Vanwolleghem, Thomas.

In: Scientific Reports, Vol. 7, No. 1, 8267, 01.12.2017.

Research output: Contribution to journalArticle

Van De Garde, MDB, Pas, SD, Van Oord, GW, Gama, L, Choi, Y, De Man, RA, Boonstra, A & Vanwolleghem, T 2017, 'Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice', Scientific Reports, vol. 7, no. 1, 8267. https://doi.org/10.1038/s41598-017-07434-y
Van De Garde, Martijn D.B. ; Pas, Suzan D. ; Van Oord, Gertine W. ; Gama, Lucio ; Choi, Youkyung ; De Man, Robert A. ; Boonstra, Andre ; Vanwolleghem, Thomas. / Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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