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Updated: Jul 20, 2025
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A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks
Published on: June 26, 2020
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Janus kinase-inhibition modulates hepatitis E virus infection
Volker Kinast1, Ioana Andreica2, Gerrit Ahrenstorf3
1Department of Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, Germany; Department for Molecular and Medical Virology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
Antiviral Research
|July 30, 2023
Summary
Janus kinase (JAK) inhibitors may increase Hepatitis E virus (HEV) replication in immunocompromised patients. Monitoring for HEV is crucial during JAK inhibitor therapy, especially with elevated liver enzymes.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Hepatitis E virus (HEV) typically causes self-limiting illness, but can become chronic and severe in immunocompromised individuals.
- Janus kinase (JAK) inhibitors are used for autoimmune inflammatory rheumatic diseases (AIRD) and impact innate immunity.
- Viral infections and reactivations are common in AIRD patients on JAK inhibitors.
Purpose of the Study:
- To investigate the effect of JAK inhibitors on HEV replication.
- To understand the mechanism by which JAK inhibitors influence HEV infection in the context of AIRD treatment.
Main Methods:
- Evaluation of liver enzymes in an AIRD patient with hepatitis E undergoing JAK inhibitor therapy.
- Infection of primary human hepatocytes (PHHs) with HEV (Kernow-C1 p6) in vitro.
- Immunofluorescence staining for viral markers and transcriptomic analysis of infected PHHs with and without JAK inhibitors.
Main Results:
- JAK inhibitor treatment led to a 50-fold increase in HEV progeny virus production in PHHs.
- Transcriptomic analysis showed altered induction of antiviral programs and interferon-stimulated genes (ISGs) in the presence of JAK inhibitors.
- Perturbation of ISG upregulation correlated with elevated HEV RNA levels, suggesting impaired antiviral response.
Conclusions:
- Therapeutic JAK inhibition appears to enhance HEV replication by modulating the host's immune response to the virus.
- Close monitoring for HEV infections is recommended in patients treated with JAK inhibitors, particularly if they present with elevated liver enzymes.
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