High-throughput mapping of virus-host interactions to identify new factors of virulence and pathogenicity for ASFV - Anses - Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail Access content directly
Conference Papers Year : 2022

High-throughput mapping of virus-host interactions to identify new factors of virulence and pathogenicity for ASFV

Abstract

African swine fever (ASF) is a highly pathogenic disease causing hemorrhagic fever in domestic pigs and wild boar. It is responsible for numerous epizootics, particularly in Europe and Asia, causing major economic losses to the swine industry. The African Swine Fever virus (ASFV) is the etiological agent responsible for this disease. It is a large double-stranded DNA virus encoding for more than 150 proteins. Different works have shown that there is a close relationship between the ability of some viral proteins to modulate the host antiviral response and the attenuation and virulence processes of ASFV. However, only few protein-protein interactions have been described so far to explain how ASFV escape the host immunity, notably by inhibiting the type I interferon (IFN-I) response. First, we used an unbiased screen to search for cellular partners of 18 viral proteins considered as important virulence factors. We performed yeast two-hybrid screens using these viral proteins of the Georgia 2007/1 strain as baits and identified more than 50 new virus-host interactions. The global analysis of these interactions clearly shows an enrichment for cellular factors involved in the cytoskeleton (KIF15, FNLB, KRT15, CENPF) and the innate immunity (COPA, TNIP2, TRIM7, CALCOCO2). In parallel, we were interested in the ability of ASFV proteins to individually inhibit the IFN-I pathway. For this purpose, we have screened 105 ASFV proteins using an IFN-luciferase reporter gene system. We showed that at least five viral proteins (I267L, MGF360-11L, DP96R, MGF505-3R and R298L) contribute to the inhibition of the IFN-I induction pathway. In order to characterize their antagonist effect, an original split-nanoluciferase approach was used to screen these viral proteins with a library of 16 major proteins of the IFN-I response. This approach led us to identify IRF3, IRF7, NEMO and TRIF as new putative targets of ASFV proteins. By combining different screening approaches, we have already highlighted new mechanisms by which ASFV hijacks cellular pathway for replication and escapes the vigilance of the immune system. Later on, by comparing virus-host interactions that have been (and will be) obtained with attenuated strains of ASFV, we should identify specific targets that could explain the attenuation process at the molecular level.
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Dates and versions

anses-04082836 , version 1 (26-04-2023)

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  • HAL Id : anses-04082836 , version 1

Cite

Juliette Dupré, Aurore Fablet, Evelyne Hutet, Soumaya Messaoudi, Yves Jacob, et al.. High-throughput mapping of virus-host interactions to identify new factors of virulence and pathogenicity for ASFV. 14th Annual Meeting EPIZONE, May 2022, Barcelone (ES), Spain. ⟨anses-04082836⟩
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