Modulation of the Tissue Expression Pattern of Zebrafish CRP-Like Molecules Suggests a Relevant Antiviral Role in Fish Skin.

Abstract

Simple SummaryThe clinical use of the human short pentraxin C-reactive protein as a health biomarker is expanded worldwide. The acute increase of the serum levels of short pentraxins in response to bacterial infections is evolutionarily conserved, as are the main functions of pentraxins. Interestingly, fish orthologs have been found to increase similarly after bacterial and viral stimuli, thus becoming promising candidates for health biomarkers of both types of infection in this group of vertebrates. To preliminarily assess their adequacy for this application, zebrafish and a fish rhabdovirus were chosen as infection model systems for the analysis of the levels of gene expression of all short pentraxins in healthy and infected animals in a wide range of tissues. Because some significant increases were found in skin (a very suitable sampling source for testing purposes), further transcript analyses were carried out in this tissue. Due to the functional similarities between pentraxins and antibodies, it was also checked whether short pentraxins can compensate for the deficiencies in adaptive immunity by using mutant zebrafish lacking this system. In conclusion, the obtained results suggest that short pentraxins are highly reactant against viruses in skin and their overexpression seems to reflect a mechanism to compensate for the loss of adaptive immunity.Recent studies suggest that short pentraxins in fish might serve as biomarkers for not only bacterial infections, as in higher vertebrates including humans, but also for viral ones. These fish orthologs of mammalian short pentraxins are currently attracting interest because of their newly discovered antiviral activity. In the present work, the modulation of the gene expression of all zebrafish short pentraxins (CRP-like proteins, CRP1-7) was extensively analyzed by quantitative polymerase chain reaction. Initially, the tissue distribution of crp1-7 transcripts and how the transcripts varied in response to a bath infection with the spring viremia of carp virus, were determined. The expression of crp1-7 was widely distributed and generally increased after infection (mostly at 5 days post infection), except for crp1 (downregulated). Interestingly, several crp transcription levels significantly increased in skin. Further assays in mutant zebrafish of recombinant activation gene 1 (rag1) showed that all crps (except for crp2, downregulated) were already constitutively highly expressed in skin from rag1 knockouts and only increased moderately after viral infection. Similar results were obtained for most mx isoforms (a reporter gene of the interferon response), suggesting a general overcompensation of the innate immunity in the absence of the adaptive one.