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Title
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Treatment induced clearance of hepatitis E viruses by interferon‐lambda in liver‐humanized mice
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Author
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Abstract
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| Background: Hepatitis E viruses (HEV) are an underestimated global cause of enterically transmitted viral hepatitis, which may persist in immunocompromised hosts, posing a risk for progressive liver fibrosis with limited treatment options. We previously established liver-humanized mice as a model for chronic HEV infections, which can be cleared by a 2-week pegylated (peg)-Interferon(IFN)α treatment course. However, severe side effects may hamper the use of IFNα in immunocompromised transplant recipient patients. IFNλ may be a valuable alternative, as its receptor is less ubiquitously expressed. Aims: In this study, we assess the in vitro and in vivo potency of pegIFNλ to induce innate immune signalling in liver cells and to clear a persistent HEV infection in liver-humanized mice. Methods & results: We found that human liver cells expressed the IFNλ receptor (IFNLR1) and are responsive to pegIFNλ. Treatment with pegIFNλ of liver-humanized mice persistently infected with HEV genotype 3 showed that pegIFNλ was well tolerated. Dose escalation studies showed that although HEV was not cleared at pegIFNλ doses up to 0.12 mg/kg for a maximum of 8 weeks, a dose of 0.3 mg/kg pegIFNλ treatment resulted in complete clearance of HEV antigen and HEV RNA from the liver in 8 out of 9 liver-humanized mice. Conclusions: PegIFNλ is well tolerated in mice and leads to clearance of a persistent HEV infection in liver-humanized mice. |
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Language
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English
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Source (journal)
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Liver international. - Copenhagen, 2003, currens
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Publication
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Copenhagen
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2021
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ISSN
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1478-3223
[print]
1478-3231
[online]
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DOI
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10.1111/LIV.15033
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Volume/pages
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41
:12
(2021)
, p. 2866-2873
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ISI
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000690754300001
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Pubmed ID
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34392598
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Full text (Publisher's DOI)
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Full text (open access)
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