期刊
NATURE MICROBIOLOGY
卷 3, 期 12, 页码 1369-1376出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41564-018-0273-9
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资金
- UK Medical Research Council [G1000196]
- Wellcome Trust [106223/Z/14/Z]
- NIH [DA033773]
- Wellcome Trust Research Training Fellowship
- National Institute for Health Research BRC King's Prize Fellowship
- Institut National de la Sante et de la Recherche Medicale
- European Research Council under the European Union [759226]
- ATIP-Avenir Program
- Centre National de la Recherche Scientifique
- France Recherche Nord & Sud Sida/HIV et Hepatites
- Ministry of Higher Education and Research
- King's College London
- Department of Health via a National Institute for Health Research BRC award
- King's College Hospital NHS Foundation Trust
- French National Research Agency [ANR-10-INBS-04]
- Montpellier University
- MRC [G1000196] Funding Source: UKRI
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA033773] Funding Source: NIH RePORTER
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 replication(1-3). Among the IFN-stimulated genes that can inhibit influenza A virus (IAV)(4) are the myxovirus resistance 1 GTPase(5) 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 endocy-tosed 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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