Dataset Information

Hydroxycholesterol binds and enhances the anti-viral activities of zebrafish monomeric c-reactive protein isoforms.

ABSTRACT: C-reactive proteins (CRPs) are among the faster acute-phase inflammation-responses proteins encoded by one gene (hcrp) in humans and seven genes (crp1-7) in zebrafish (Danio rerio) with importance in bacterial and viral infections. In this study, we described novel preferential bindings of 25-hydroxycholesterol (25HOCh) to CRP1-7 compared with other lipids and explored the antiviral effects of both 25HOCh and CRP1-7 against spring viremia carp virus (SVCV) infection in zebrafish. Both in silico and in vitro results confirmed the antiviral effect of 25HOCh and CRP1-7 interactions, thereby showing that the crosstalk between them differed among the zebrafish isoforms. The presence of oxidized cholesterols in human atherosclerotic plaques amplifies the importance that similar interactions may occur for vascular and/or neurodegenerative diseases during viral infections. In this context, the zebrafish model offers a genetic tool to further investigate these interactions.

SUBMITTER: Bello-Perez M

PROVIDER: S-EPMC6336239 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hydroxycholesterol binds and enhances the anti-viral activities of zebrafish monomeric c-reactive protein isoforms.

Bello-Perez Melissa M Falco Alberto A Novoa Beatriz B Perez Luis L Coll Julio J

PloS one 20190117 1

C-reactive proteins (CRPs) are among the faster acute-phase inflammation-responses proteins encoded by one gene (hcrp) in humans and seven genes (crp1-7) in zebrafish (Danio rerio) with importance in bacterial and viral infections. In this study, we described novel preferential bindings of 25-hydroxycholesterol (25HOCh) to CRP1-7 compared with other lipids and explored the antiviral effects of both 25HOCh and CRP1-7 against spring viremia carp virus (SVCV) infection in zebrafish. Both in silico ...[more]

PMID: 30653529

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Project description:Oxysterol-binding Protein (OSBP) is a human lipid-transport protein required for the cellular replication of many types of viruses, including several human pathogens. The structurally-diverse small molecule compounds OSW-1, itraconazole (ITZ), T-00127-HEV2 (THEV) and TTP-8307 (TTP) inhibit viral replication through interaction with the OSBP protein. The OSW-1 compound reduces intracellular OSBP, and the reduction of OSBP protein levels persists multiple days after the OSW-1-compound treatment is stopped. The OSW-1-induced reduction of OSBP levels inhibited Enterovirus replication prophylactically in cells. In this report, the OSBP-interacting compounds ITZ, THEV, and TTP are shown not to reduce OSBP levels in cells, unlike the OSW-1-compound, and the OSW-1 compound is determined to be the only compound capable of providing prophylactic antiviral activity in cells. Furthermore, OSW-1 and THEV inhibit the binding of 25-hydroxycholesterol (25-OHC) to OSBP indicating that these compounds bind at the conserved sterol ligand binding site. The ITZ and TTP compounds do not inhibit 25-hydroxycholesterol binding to OSBP, and therefore ITZ and TTP interact with OSBP through other, unidentified binding sites. Co-administration of the THEV compound partially blocks the cellular activity of OSW-1, including the reduction of cellular OSBP protein levels; co-administration of the ITZ and TTP compounds have minimal effect on OSW-1 cellular activity further supporting different modes of interaction with these compounds to OSBP. OSW-1, ITZ, THEV, and TTP treatment alter OSBP cellular localization and levels, but in four distinct ways. Co-administration of OSW-1 and ITZ induced OSBP cellular localization patterns with features similar to the effects of ITZ and OSW-1 treatment alone. Based on these results, OSBP is capable of interacting with multiple structural classes of antiviral small molecule compounds at different binding sites, and the different compounds have distinct effects on OSBP cellular activity.

Dataset Information

Hydroxycholesterol binds and enhances the anti-viral activities of zebrafish monomeric c-reactive protein isoforms.

Publications

Hydroxycholesterol binds and enhances the anti-viral activities of zebrafish monomeric c-reactive protein isoforms.

Similar Datasets

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