JAK inhibitors remove innate immune barriers facilitating viral propagation
Janus kinase (JAK) inhibitors are small-molecule therapeutics that reduce inflammation in autoimmune and inflammatory diseases by modulating the JAK-STAT pathway. While effective in alleviating immune-mediated conditions, JAK inhibitors can impair antiviral defences by suppressing interferon (IFN) responses, potentially increasing susceptibility to viral infections. This study investigates the pro-viral mechanism of JAK inhibitors, focusing on baricitinib, across various cell lines, organoids, and viral strains, including a recombinant Rift Valley fever virus, influenza A virus, SARS-CoV-2, and wild-type adenovirus. Our findings demonstrate that baricitinib suppresses transcription of IFN-stimulated genes in non-infected cells, which is triggered by type I IFNs produced by infected cells, facilitating viral propagation. The pro-viral effect was influenced by viral load, inhibitor concentration, and structural characteristics of the compound. These results underscore the dual effects of JAK inhibitors: reducing inflammation while potentially exacerbating viral infections. Additionally, the findings highlight opportunities to leverage JAK inhibitors for viral research, vaccine production, and drug screening.
Authors
- Magnar Bjørås (ORCID: https://orcid.org/0000-0001-8759-1170)
- Erlend Ravlo
- Valentyn Oksenych (ORCID: https://orcid.org/0000-0002-5088-3791)
- Olli Vapalahti (ORCID: https://orcid.org/0000-0003-2270-6824)
- Teemu Smura (ORCID: https://orcid.org/0000-0002-9187-3151)
- Ole Solheim (ORCID: https://orcid.org/0000-0002-5954-4817)
- Janne Fossum Malmring
- Hilde Lysvand
- Magnus Evander (ORCID: https://orcid.org/0000-0001-6034-4807)
- Aleksandr Ianevski (ORCID: https://orcid.org/0000-0002-7780-482X)
- Mårten Strand
- Jan Egil Afset (ORCID: https://orcid.org/0000-0003-2489-4179)
- Miroslava Kiššová (ORCID: https://orcid.org/0000-0001-9798-9131)
- Friedemann Weber (ORCID: https://orcid.org/0000-0001-9737-337X)
- Jørn-Ove Schjølberg
- Wei Wang (ORCID: https://orcid.org/0000-0002-8696-9773)
- Denis E. Kainov
- Hanna Vauhkonen (ORCID: https://orcid.org/0000-0002-5708-6680)
- Marius Nårstad Skipperstøen
- Marthe Vestvik
Institutions
- Oslo University Hospital (NO)
- University of Helsinki (FI)
- Norwegian University of Science and Technology (NO)
- Helsinki University Hospital (FI)
- St Olav's University Hospital (NO)
- Department of Embryology (US)
- Institute for Molecular Medicine Finland (FI)
- Institute of Virology of the Slovak Academy of Sciences (SK)
- Umeå University (SE)
Publication Details
- Journal
- NAR Molecular Medicine
- Published
- 2025-03-29
- DOI
- https://doi.org/10.1093/narmme/ugaf017
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Vetenskapsrådet
- Helse Midt-Norge
- St. Olavs Hospital Universitetssykehuset i Trondheim