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

TY - JOUR

T1 - The interferon inducible isoform of NCOA7 inhibits endosome-mediated viral entry

AU - Doyle, Tomas

AU - Moncorgé, Olivier

AU - Bonaventure, Boris

AU - Pollpeter, Darja

AU - Lussignol, Marion

AU - Tauziet, Marine

AU - Apolonia, Luis

AU - Catanese, Maria Teresa

AU - Goujon, Caroline

AU - Malim, Michael

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of interferon-stimulated genes (ISGs) whose products interact with viral components or alter cellular physiology to suppress viral replication (1-3). Among the ISGs that can inhibit influenza A virus (IAV) (4) are the myxovirus resistance 1 (MX1) GTPase (5) and IFN-induced transmembrane protein 3 (IFITM3) (6, 7). Here we use ectopic expression and gene knock-out 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 (HCV). 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 (vRNPs). NCOA7, therefore, provides a mechanism for immune regulation of endo-lysosomal 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.

AB - Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of interferon-stimulated genes (ISGs) whose products interact with viral components or alter cellular physiology to suppress viral replication (1-3). Among the ISGs that can inhibit influenza A virus (IAV) (4) are the myxovirus resistance 1 (MX1) GTPase (5) and IFN-induced transmembrane protein 3 (IFITM3) (6, 7). Here we use ectopic expression and gene knock-out 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 (HCV). 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 (vRNPs). NCOA7, therefore, provides a mechanism for immune regulation of endo-lysosomal 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.

U2 - 10.1038/s41564-018-0273-9

DO - 10.1038/s41564-018-0273-9

M3 - Article

SN - 2058-5276

VL - 3

SP - 1369

EP - 1376

JO - Nature Microbiology

JF - Nature Microbiology

IS - 12

ER -