The cellular activating protein-1 cFos regulates influenza A virus replication

TL;DR

This study shows that the protein cFos helps influenza A virus replicate in human lung cells by reducing cell death and immune responses.

Contribution

The novel finding is that cFos, an AP-1 transcription factor, acts as a proviral factor for influenza A virus by modulating innate immunity and apoptosis.

Findings

cFos knockdown impairs influenza A virus replication in A549 cells.

cFos supports viral replication by reducing apoptosis and interferon-β expression.

cFos knockdown decreases viral NA mRNA and late viral protein expression.

Abstract

Previous research has demonstrated that influenza A virus (IAV) infection activates activating protein-1 (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-β mRNA levels in cFos–knockdown A549 cells during IAV infection. This suggests that cFos may enhance cell survival and reduce interferon-β 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.

Figures