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 : 2022

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

Morgan Sarry
Souheyla Benfrid
Cindy Bernelin-Cottet
  • Fonction : Auteur
Anthony Relmy
  • Fonction : Auteur
  • PersonId : 1075108
Aurore Romey
Anne-Laure Salomez
  • Fonction : Auteur
Stéphan Zientara
Damien Vitour
  • Fonction : Auteur
  • PersonId : 1136800
Sandra Blaise-Boisseau

Résumé

Introduction One of the problems associated with Foot-and-Mouth disease is the ability of FMDV (Foot-and-Mouth Disease Virus) to persist in infected ruminants for several months. Despite considerable work done to date, the underlying mechanisms remain unknown. However, we have shown in a previous collaborative project that persistent infection in bovine primary cells is associated with a durable but attenuated and 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 described 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. Materials and methods In this project we focused on the interplay between FMDV proteins and 16 cellular proteins belonging to the type I interferon (IFN I) pathway, which are 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 FMDV O/FRA/1/2001 Clone 2.2 proteins were produced by Gateway method. PPI were identified under overexpression condition in HEK293T cells by NanoLuc-2-Hybrid screening and verified 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 numerous PPI between the IFN pathway proteins and the viral proteins tested. 3A, 3C and 3D are the viral proteins for which the greatest number of interactors were identified. The most promising results concern the 3D polymerase for which no interaction with the IFN pathway has been described so far. This protein was used to screen cattle, sheep, goat and pig NanoLuc plasmid libraries. When comparing the results of these screens, it appears that most of the interactors are shared with relative strength across species as illustrated in figure 1. The FMDV-host PPI, have been confirmed by affinity chromatography GST Pull-Down for the four species and functional validation of these PPI is ongoing. Furthermore, we have demonstrated by luciferase reporter assays the inhibitory effect of 3D polymerase on the induction phase of the IFN response. Discussion With this study, we have demonstrated novel interactions between some FMDV proteins, including 3D, and cellular proteins involved in the IFN pathway from four virus-susceptible species. A direct effect of 3D on the IFN pathway induction stage was also revealed. Combined, these results strongly suggest that 3D polymerase could play an unsuspected role in the FMDV escape from the host IFN response. A modulation of the antiviral response by the FMDV, through interactions with its host, is one of the hypotheses explored to understand FMDV persistence. Thus, it is entirely conceivable that the 3D protein, by interacting with certain proteins of the IFN pathway, may contribute to the establishment and/or maintenance of a virus-host equilibrium.
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Dates et versions

anses-04524003 , version 1 (27-03-2024)

Identifiants

  • HAL Id : anses-04524003 , version 1

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Morgan Sarry, Souheyla Benfrid, Cindy Bernelin-Cottet, Anthony Relmy, Aurore Romey, et al.. Interplay between Foot-and-Mouth Disease Virus 3D polymerase and the type I interferon response: a contribution to viral persistence?. OPEN SESSION EuFMD, EuFMD, Oct 2022, Marseille, France. ⟨anses-04524003⟩
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