The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry

Abstract : Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of IFN-stimulated genes whose products interact with viral components or alter cellular physiology to suppress viral replication1-3. Among the IFN-stimulated genes that can inhibit influenza A virus (IAV)4 are the myxovirus resistance 1 GTPase5 and IFN-induced transmembrane protein 3 (refs 6,7). Here, we use ectopic expression and gene knockout to demonstrate that the IFN-inducible 219-amino acid short isoform of human nuclear receptor coactivator 7 (NCOA7) is an inhibitor of IAV as well as other viruses that enter the cell by endocytosis, including hepatitis C virus. NCOA7 interacts with the vacuolar H+-ATPase (V-ATPase) and its expression promotes cytoplasmic vesicle acidification, lysosomal protease activity and the degradation of endocytosed antigen. Step-wise dissection of the IAV entry pathway demonstrates that NCOA7 inhibits fusion of the viral and endosomal membranes and subsequent nuclear translocation of viral ribonucleoproteins. Therefore, NCOA7 provides a mechanism for immune regulation of endolysosomal physiology that not only suppresses viral entry into the cytosol from this compartment but may also regulate other V-ATPase-associated cellular processes, such as physiological adjustments to nutritional status, or the maturation and function of antigen-presenting cells.
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Tomas Doyle, Olivier Moncorgé, Boris Bonaventure, Darja Pollpeter, Marion Lussignol, et al.. The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry. Nature Microbiology, Nature Publishing Group, 2018, 3 (12), pp.1369-1376. ⟨10.1038/s41564-018-0273-9⟩. ⟨inserm-02137167⟩

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