SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus
Abstract
Interferon-induced antiviral proteins act on the first line of defence against viruses, including influenza A virus (IAV). Among those, the short isoform of Nuclear Receptor Coactivator 7 (NCOA7-AS) has been shown to inhibit IAV entry and more especially the fusion between endosomal and viral membranes. Ectopic expression of NCOA7-AS leads to the increased acidification of the endolysosomal pathway, putatively through NCOA7-AS interaction with the vacuolar ATPase (V-ATPase). However, the precise mechanism of action of NCOA7-AS is not fully understood. Here, we identified the cellular partners of NCOA7-AS by mass spectrometry, including the V-ATPase subunits known to interact with NCOA7-AS. A point mutation disrupting the interaction with the V-ATPase led to loss of antiviral activity against IAV, demonstrating that V-ATPase engagement is required for the antiviral phenotype. Moreover, sorting nexin (SNX) 1/2/5/6 were identified as novel partners of NCOA7-AS. These proteins are involved in retrograde transport of cellular cargoes from endosomes to the trans-Golgi network. We revealed that SNX5/6 interacted directly with NCOA7-AS and were essential for NCOA7-AS antiviral activity against IAV. Interestingly, crystal structures of NCOA7-AS/SNX5 complexes showed that the SNX5-interaction motif in NCOA7-AS was similar to those found in known cargoes of SNX5/6. In addition, we could pinpoint several critical residues that were important for binding and antiviral activity. Collectively, our study identifies novel essential partners for NCOA7-AS antiviral activity and the structural basis for their interaction.
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BibTeX
@article{arnaudarnould2026snxbar,
title = {{SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus}},
author = {Mary Arnaud-Arnould and Antoine Rebendenne and Marine Tauziet and Serge Urbach and Khadija El Koulali and Emiliano P Ricci and Mélanie Wencker and Olivier Moncorgé and Mickaël Blaise and Caroline Goujon},
journal = {Journal of Biological Chemistry},
year = {2026},
month = sep,
doi = {10.1016/j.jbc.2026.113372},
url = {https://hal.science/hal-05722248v2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus
AU - Mary Arnaud-Arnould
AU - Antoine Rebendenne
AU - Marine Tauziet
AU - Serge Urbach
AU - Khadija El Koulali
AU - Emiliano P Ricci
AU - Mélanie Wencker
AU - Olivier Moncorgé
AU - Mickaël Blaise
AU - Caroline Goujon
PY - 2026
DA - 2026/09/24
JO - Journal of Biological Chemistry
DO - 10.1016/j.jbc.2026.113372
UR - https://hal.science/hal-05722248v2
AB - Interferon-induced antiviral proteins act on the first line of defence against viruses, including influenza A virus (IAV). Among those, the short isoform of Nuclear Receptor Coactivator 7 (NCOA7-AS) has been shown to inhibit IAV entry and more especially the fusion between endosomal and viral membranes. Ectopic expression of NCOA7-AS leads to the increased acidification of the endolysosomal pathway, putatively through NCOA7-AS interaction with the vacuolar ATPase (V-ATPase). However, the precise mechanism of action of NCOA7-AS is not fully understood. Here, we identified the cellular partners of NCOA7-AS by mass spectrometry, including the V-ATPase subunits known to interact with NCOA7-AS. A point mutation disrupting the interaction with the V-ATPase led to loss of antiviral activity against IAV, demonstrating that V-ATPase engagement is required for the antiviral phenotype. Moreover, sorting nexin (SNX) 1/2/5/6 were identified as novel partners of NCOA7-AS. These proteins are involved in retrograde transport of cellular cargoes from endosomes to the trans-Golgi network. We revealed that SNX5/6 interacted directly with NCOA7-AS and were essential for NCOA7-AS antiviral activity against IAV. Interestingly, crystal structures of NCOA7-AS/SNX5 complexes showed that the SNX5-interaction motif in NCOA7-AS was similar to those found in known cargoes of SNX5/6. In addition, we could pinpoint several critical residues that were important for binding and antiviral activity. Collectively, our study identifies novel essential partners for NCOA7-AS antiviral activity and the structural basis for their interaction.
SN - 0021-9258
SN - 1083-351X
ER -