Mij
Senior Member (Voting Rights)
Abstract
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 defenses 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, retinal organoids, and viral strains, including a recombinant IFN-sensitive Rift Valley fever (rRVFV), influenza A (rIAV), SARS-CoV-2 (rSARSCoV-2) reporter viruses, and wild type adenovirus (AdV).
Our findings demonstrate that baricitinib suppresses transcription of IFN-stimulated genes in non-infected cells (ISGs) which is triggered by type I IFNs produced by infected cells, facilitating viral propagation. The pro-viral effects were 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.
LINK
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 defenses 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, retinal organoids, and viral strains, including a recombinant IFN-sensitive Rift Valley fever (rRVFV), influenza A (rIAV), SARS-CoV-2 (rSARSCoV-2) reporter viruses, and wild type adenovirus (AdV).
Our findings demonstrate that baricitinib suppresses transcription of IFN-stimulated genes in non-infected cells (ISGs) which is triggered by type I IFNs produced by infected cells, facilitating viral propagation. The pro-viral effects were 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.
LINK