Study of the Antiviral Immune Response of Zebrafish (Danio rerio) against the Hemorrhagic Virus SVCV

Résumé

Innate immunity is the organism´s first line of defence against pathogens and infections. It is characterized by pre-established, relatively unspecific and fast actions. The genes that take part in the innate immunity are fully coded in the genome and generally non-modified during the lifespan of the organism. Understand the complex mechanisms through which viruses modulate immune function should provide key information aimed to develop a range of potential targeted antiviral therapies. The aim of this doctoral thesis is the characterisation of zebrafish antiviral response against the hemorrhagic virus spring viraemia of carp virus (SVCV), in order to know the molecules involved and deepen the knowledge of the inflammatory response caused by the pathogen (responsible cells, cell migration, genes and gene circuits involved). The overall objective of this research is the identification of key genes in the process of defence against SVCV in zebrafish, to learn more about the pathology generated from an immunological point of view. This thesis is structured in two sections. First one (Chapters 3, 4 and 5), deals with the characterisation of the expression and function of genes involved in the antiviral immune response. Second section (Chapters 6 and 7), concerns the study of the immune and inflammatory responses caused by SVCV in zebrafish larvae. In order to improve or complete the knowledge about the signalling pathways induced in response to a virus several genes that participate in the innate antiviral response in zebrafish were characterised. Moreover, with the objective of improving the knowledge of the pathology generated by SVCV, a systemic infection was stablished in zebrafish larvae as a model of hemorrhagic disease,. As host-pathogen interactions are essential for the modulation of the immune response during an infection, the leukocyte dynamic and the inflammatory response during the infection with SVCV were also studied using zebrafish larvae.