Interplay between Foot-and-Mouth Disease Virus 3D polymerase and the type I interferon response: a contribution to viral persistence? - Anses - Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail Accéder directement au contenu
Communication Dans Un Congrès Année : 2023

Interplay between Foot-and-Mouth Disease Virus 3D polymerase and the type I interferon response: a contribution to viral persistence?

Résumé

Background and Objectives One important issue associated with Foot-and-Mouth disease (FMD) is the ability of FMD virus to persist in ruminants for several months. Despite considerable work done, the underlying mechanisms remain unknown. However, we have shown previously that persistent infection in bovine primary cells is associated with a durable but ineffective innate antiviral response that may rely on protein-protein interactions (PPI) between FMDV and its host. While FMDV persistence has been reported in ruminants, it has not been reported in pigs. This differential persistence provides an opportunity to compare virus-host interactions between species, determine their host specificity and identify potential links between PPI and viral persistence. Material and Methods We focused on the interplay between FMDV proteins and 16 cellular proteins belonging to the type-I interferon (IFN I) pathway, described as involved in more than 75% of virus-host PPI. Plasmids expressing these 16 proteins from cattle, pig, sheep and goat, as well as expression vectors for the 15 serotype-O FMDV proteins were built by Gateway method. PPI were identified by NanoLuc-2-Hybrid screening and confirmed using affinity chromatography GST-Pull-Down. The phenotypic impact of some FMDV proteins on the IFN pathway has also been investigated via luciferase reporter assays. Results The NanoLuc-2-Hybrid approach revealed several PPI between the IFN pathway proteins and the viral proteins tested. The most promising results concerned the 3Dpol for which no interaction with the IFN pathway has been described. This protein was used to screen cattle, sheep, goat and pig NanoLuc plasmid libraries. When comparing the screening results, it appears that most of the interactors are shared with relative strength across species. The FMDV-host PPI have been confirmed by GST-Pull-Down and functional validation is ongoing. Furthermore, we have demonstrated by luciferase reporter assays the inhibitory effect of 3Dpol on the IFN pathway induction phase. Conclusion We have demonstrated novel interactions between FMDV 3Dpol and cellular proteins involved in the IFN pathway from four virus-susceptible species. A direct effect of 3Dpol on the IFN pathway induction phase was also revealed. Combined, these results strongly suggest that 3Dpol could play an unsuspected role in FMDV escape from the host IFN pathway. A FMDV modulation of the antiviral response, through interactions with its host, is one hypothesis explored to understand FMDV persistence. Thus, it is conceivable that the 3Dpol protein, by interacting with certain IFN pathway proteins, might contribute to the establishment and/or maintenance of a FMDV-host equilibrium.
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Dates et versions

anses-04426436 , version 1 (30-01-2024)

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Paternité - Pas de modifications

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  • HAL Id : anses-04426436 , version 1

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Morgan Sarry, Grégory Caignard, Juliette Dupre, Stéphan Zientara, Damien Vitour, et al.. Interplay between Foot-and-Mouth Disease Virus 3D polymerase and the type I interferon response: a contribution to viral persistence?. Epizone, 15th annual meeting 2023, EPIZONE European Research Group, Apr 2023, Novi Sad, Serbia. ⟨anses-04426436⟩
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