Study of immune innate cell migration in a zebrafish model infected with Orthobunyavirus oropoucheense

Abstract

Orthobunyavirus oropoucheense (OROV) is responsible for Oropouche fever, which caused numerous outbreaks and affected more than half a million people in Latin America since its discovery in Trinidad and Tobago in 1955. OROV is classified as a member of the Orthobunyavirus genus, which comprises viruses concerning One-health issues, such as Schmallenberg, Akabane and Bunyamwera orthobunyavirus. These viruses are known as arthropod-borne viruses (or arboviruses), representing an increasing concern due to climate changes and the potential transmission caused by the increasing distribution of arthropods. The understanding of the interactions between orthobunyavirus and host cells remains incomplete, leading to a limited comprehension of its immunopathology and the underlying causes of the symptoms experienced by patients. Therefore, we aim to elucidate the dynamics between OROV, and the host innate immune response using zebrafish larvae (Danio rerio) as a model. Zebrafish offer advantages in the study of infectious diseases as it has transparent embryos, a diverse number of transgenic lineages and shared genomic homology with humans, which provides a range of tools to study immunopathogenesis. Notably, zebrafish larvae lack an adaptive immune system within their initial ~6 weeks post-fertilization, allowing focused investigation into the innate immune response. Thus, our objective is to comprehend the migration and recruitment of macrophages and neutrophils to the Central Nervous System of zebrafish during OROV infection. Despite of its medical importance, there are no vaccine or specific treatment for Orthobunyavirus infection. For this reason, studies into host-pathogen dynamics could unveil insights into viral infections and innate immune responses throughout the infection course, contributing to the development of strategies for Oropouche fever treatment or prophylaxis.