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bioRxiv · 10.1101/2025.08.12.669837

The cellular Activating Protein 1 cFos regulates Influenza A virus replication

Gerodez, A.·Dufrasne, F. E.·Denis, O.·Steensels, M.·Lambrecht, B.·Tafforeau, L.·Demeret, C.·Barbezange, C.
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Abstract

Previous research has demonstrated that Influenza A virus (IAV) infection activates AP-1 transcription factors as part of the antiviral response. In this study, we identified cFos as the most upregulated AP-1 transcription factor during IAV infection in A549 human lung cells. Surprisingly, the knockdown of cFos resulted in impaired IAV replication. Fluorescence microscopy and functional analyses indicated that cFos is implicated in IAV infection through its nuclear function, rather than its cytoplasmic role as an activator of lipid synthesis. The investigation into the role of cFos in IAV infection revealed increased apoptosis and elevated interferon-{beta} mRNA levels in cFos-knockdown A549 cells during IAV infection. This suggests that cFos may enhance cell survival and reduce interferon-{beta} expression during infection, thereby facilitating IAV proliferation. Furthermore, the levels of viral NA mRNA and the expression of late viral proteins NA and M2 decreased upon cFos knockdown. Overall, this study identifies cFos as a proviral factor for IAV, through the modulation of innate immunity and apoptosis during infection, and potentially by supporting the viral transcription. Author SummaryInfluenza A viruses pose a significant threat to global public health. Understanding the interaction between the virus and host is essential for the development of antiviral therapies. We identified cFos, a cellular Activating Protein-1, as a pro-viral factor for influenza A viruses. cFos was found to enhance cell survival and regulate the expression of certain cytokines during viral infection. Our findings also suggested a potential role for cFos in the viral transcription, especially of the viral proteins expressed late in the viral cycle.

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Gerodez, A., Dufrasne, F. E., Denis, O., Steensels, M., Lambrecht, B., Tafforeau, L., Demeret, C., Barbezange, C.. 2025-08-12. The cellular Activating Protein 1 cFos regulates Influenza A virus replication. https://doi.org/10.1101/2025.08.12.669837

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