VirIVITES · ARBOVIRUS SKIN INFECTION MODELLING FOR MORE ACCURATE VIRAL PATHOGENESIS

ARBOVIRUS SKIN INFECTION MODELLING FOR MORE ACCURATE VIRAL PATHOGENESIS

Arthropods, such as mosquitoes, are responsible for the transmission of viruses (arboviruses) to humans, while blood feeding on the skin. These viruses, causing more than a 100 million of symptomatic infections per year, are accountable for over 40 thousand deaths each year worldwide. The ill effects associated to these diseases, are a burden for the patients and for the economy of the affected countries. Furthermore, the geographical distribution of the vectors, and de facto of their associated diseases, is changing owing to convergence of multiple factors including globalization and global warming. Despite advances in public health awareness, little medical advancements have been made. One reason for such slow biomedical progress is the lack of adequate research models. In that sense, one alternative could be the use of organoids. Defined as self-organizing tridimensional cell cultures, organoids have already proven to be useful in the study of human diseases including viral infection. However, their use to study arbovirus skin infection had never been achieved so far. The overall aim of this research project was to establish an experimental workflow demonstrating that human skin organoids could be used to study arboviruses infection. The first step and aim consisted into the in vitro generation of reconstructed human skins and their characterisation. Once this step validated, the second aim was to determine the experimental conditions in order to have infected mosquitoes probing the engineered tissues. Finally, the last aim was to confirm and explore the infection of the tissues in order to validate the possibility of using skin organoids to study arbovirus cutaneous infection. At the end of the period allocated to this project, we have demonstrated that human skin organoids can be use in research to explore cutaneous infection by arboviruses delivered through the bite of mosquitoes. We put together an experimental workflow including the generation of human skin equivalents, the infection of mosquitoes with ZIKA and Sindbis viruses and the productive infection of the tissues exposed to the infected mosquitoes. This new research model opens unprecedented venues in the exploration of pathophysiological mechanisms involved in arbovirus skin infection in humans and to test new therapeutic approaches to counter these infections.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз