Common and species-specific molecular signatures, networks, and regulators of influenza virus infection in mice, ferrets, and humans

Molecular responses to influenza A virus (IAV) infections vary between mammalian species. To identify conserved and species-specific molecular responses, we perform a comparative study of transcriptomic data derived from blood cells, primary epithelial cells, and lung tissues collected from IAV-infected humans, ferrets, and mice. The molecular responses in the human host have unique functions such as antigen processing that are not observed in mice or ferrets. Highly conserved gene coexpression modules across the three species are enriched for IAV in fection-induced pathways including cell cycle and interferon (IFN) signaling. TDRD7 is predicted as an IFN-inducible host factor that is up-regulated upon IAV infection in the three species. TDRD7 is required for antiviral IFN response, potentially modulating IFN signaling via the JAK/STAT/IRF9 pathway. Identification of the common and species-specific molecular signatures, networks, and regulators of IAV infection provides insights into host-defense mechanisms and will facilitate the development of novel therapeutic interventions against IAV infection.

Automated summary

This study compares the molecular responses to influenza A virus infection in humans, ferrets, and mice, and identifies both conserved and species-specific molecular responses. Human hosts have unique antigen processing functions, while highly conserved gene coexpression modules across the three species are associated with cell cycle and interferon signaling pathways. TDRD7 is identified as an IFN-inducible host factor that is up-regulated in response to IAV infection in all three species, potentially modulating IFN signaling via the JAK/STAT/IRF9 pathway.