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

tetano

Editor, Senior Moderator
Sci Adv


. 2022 Oct 7;8(40):eabm5859.
doi: 10.1126/sciadv.abm5859. Epub 2022 Oct 5.
Common and species-specific molecular signatures, networks, and regulators of influenza virus infection in mice, ferrets, and humans


Christian V Forst[SUP] 1 2 3 4 [/SUP], Laura Martin-Sancho[SUP] 5 [/SUP], Shashank Tripathi[SUP] 6 [/SUP], Guojun Wang[SUP] 7 [/SUP], Luiz Gustavo Dos Anjos Borges[SUP] 4 [/SUP], Minghui Wang[SUP] 1 2 3 [/SUP], Adam Geber[SUP] 8 [/SUP], Lauren Lashua[SUP] 8 [/SUP], Tao Ding[SUP] 8 [/SUP], Xianxiao Zhou[SUP] 1 2 3 [/SUP], Chalise E Carter[SUP] 9 [/SUP], Giorgi Metreveli[SUP] 4 [/SUP], Ariel Rodriguez-Frandsen[SUP] 5 [/SUP], Matthew D Urbanowski[SUP] 4 [/SUP], Kris M White[SUP] 4 10 [/SUP], David A Stein[SUP] 11 [/SUP], Hong Moulton[SUP] 11 [/SUP], Sumit K Chanda[SUP] 5 [/SUP], Lars Pache[SUP] 5 [/SUP], Megan L Shaw[SUP] 4 [/SUP], Ted M Ross[SUP] 9 [/SUP], Elodie Ghedin[SUP] 8 12 [/SUP], Adolfo García-Sastre[SUP] 4 10 13 14 15 [/SUP], Bin Zhang[SUP] 1 2 3 [/SUP]



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Free article

Abstract

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 infection-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.
 
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