Communication Dans Un Congrès Année : 2024

SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus

Khadija El Koulali

Résumé

Seasonal influenza A viruses (IAV) are a major global health threat, applying an important pressure on health systems and causing significant morbidity and mortality each year. Interferon-induced antiviral proteins act on the first line of defense against IAV. Among those, we have shown that the short isoform of Nuclear Receptor Coactivator 7 (NCOA7-AS) inhibits IAV entry (Doyle et al, Nat Microb 2018). Overexpression of NCOA7-AS leads to the increased acidification of the endolysosomal pathway, through NCOA7-AS interaction with the vacuolar (v-)ATPase. Interestingly, NCOA7-AS overexpression was associated with a decrease in IAV/endolysosomal membrane fusion. 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. Mutation of NCOA7-AS Glycine 91 abolishes v-ATPase binding and antiviral activity against IAV, confirming the role of the v-ATPase in 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 to the trans-golgi network. We revealed that SNX5/6 were important for NCOA7-AS antiviral activity against IAV and interacted directly with NCOA7-AS. 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. Moreover, a potential link with the autophagy pathway is currently being explored. Overall, this study sheds light on how NCOA7-AS could hijack some SNX proteins to inhibit IAV replication.

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Dates et versions

hal-05192460 , version 1 (30-07-2025)

Identifiants

  • HAL Id : hal-05192460 , version 1

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Mary Arnaud-Arnould, Antoine Rebendenne, Marine Tauziet, S Urbach, Khadija El Koulali, et al.. SNX-BAR proteins 5 and 6 are required for NCOA7-AS antiviral activity against influenza A virus. Innasco Symposium, Jun 2024, Montpellier (France), France. ⟨hal-05192460⟩
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