Dataset Information

Insights into the role of VPS39 and its interaction with CP204L and A137R in ASFV infection

ABSTRACT: The African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly le-thal disease in swine, for which no antiviral drugs or vaccines are currently available. Studying viral–host protein-protein interactions advances our understanding of the molecular mecha-nisms underlying viral replication and pathogenesis and can facilitate the discovery of antiviral therapeutics. In this study, we employed affinity tagging and purification mass spectrometry to characterize the interactome of VPS39, an important cellular factor during the early phase of ASFV replication. The interaction network of VPS39 revealed associations with mitochondrial proteins involved in membrane contact sites formation and cellular respiration. We show that ASFV proteins CP204L and A137R target VPS39 by interacting with its clathrin heavy chain func-tional domain. Furthermore, we elaborate on the potential mechanisms by which VPS39 may contribute to ASFV replication and prioritize interactions for further investigation into mito-chondrial protein function in the context of ASFV infection.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Epithelial Cell

DISEASE(S): Disease Free

SUBMITTER: Katarzyna Dolata

LAB HEAD: Axel Karger

PROVIDER: PXD054169 | Pride | 2024-09-17

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	KaDo_7.10_VPS39-EGFP_1_Slot1-48_1_1160.zip	Other
	KaDo_7.10_VPS39-EGFP_2_Slot1-49_1_1161.zip	Other
	KaDo_7.10_VPS39-EGFP_3_Slot1-50_1_1162.zip	Other
	KaDo_7.10_VPS39-EGFP_4_Slot1-51_1_1163.zip	Other
	KaDo_7.10_VPS39-EGFP_asfv_1_Slot1-52_1_1166.zip	Other

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Project description:African swine fever virus (ASFV) is an infectious disease with a mortality rate of nearly 100% in pigs; however, no safe commercial vaccines or antiviral drugs are currently available, which seriously threatens the global pig industry. Therefore, effective biologicals against ASFV are urgently needed. Here, we screened 138 Bacillus subtilis strains, four of which evidently inhibited ASFV replication in vitro. Pigs fed with biologics of different types from the four B. subtilis strains showed reduced pathological changes and viral loads in tissues, with a survival rate of up to 100%. The antiviral activity of B. subtilis was attributed to small-molecule metabolites, rather than to secretory proteins. A total of 169 small molecules were obtained from the metabolites of B. subtilis using LC-MS/MS, arctiin and genistein, which showed the highest inhibition efficiency, suppressing ASFV proliferation at the mid-stage of infection. These molecules acted as competitive inhibitors by complexing the ATP-binding domain of viral topoisomerase II, as demonstrated using molecular docking, biolayer interferometry binding and a competitive decatenation assay, thereby disrupting the catalytic activity of the enzyme and inhibiting ASFV replication. Furthermore, pigs administered arctiin and genistein orally showed decreased mortality and tissue damage. Collectively, these results suggest that the four B. subtilis strains screened may be preventative biologicals against ASFV infection. Our findings pave the way for ASFV prevention and control strategies in the pig industry to curb the economic losses caused by the disease. IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologicals or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

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Insights into the role of VPS39 and its interaction with CP204L and A137R in ASFV infection

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