25-HYDROXYL-CHOLESTEROL BINDS AND ENHANCE ANTI-VIRAL EFFECTS OF ZEBRAFISH MONOMERIC C-REACTIVE PROTEINS

Abstract

C-reactive proteins (CRP) are among the faster acute-phase inflammation-responses coded by one gene in humans (hcrp) and seven genes (crp1-7) in zebrafish (Danio rerio). In this study, preferential 25-hydroxycholesterol (25HOCh) binding to zebrafish CRP1-7 compared to other lipids were predicted by in silico docking and confirmed by solid-phase binding-assays. In addition, 25HOCh enhanced methyl-betacyclodextrin-sensitive (Cholesterol-dependent) CRP1-7 anti-viral effects in a fine-tunned isoform-dependent manner. In silico and structural studies suggested that the crosstalk between the anti-viral enhancements of both 25HOCh and CRP1-7 were dependent on protein monomers rather than oligomers but differred among isoforms. The presence of oxidized cholesterols in human atherosclerotic plaques amplifies the importance that similar interactions may have for vascular and/or neurodegenerative diseases during viral infections. In this context, the zebrafish model offers a genetic tool to further investigate how the expression and functions of different CRP isoforms and/or transcript variants may be controlled.