INvestigating Transmission and Early Replication of Rift valley fever viruS following mosquito Exposure in Cutaneous Tissue

Vector-borne viruses (arboviruses) pose an increasing global threat, causing widespread disease in both humans and animals with significant health and economic impacts. In Europe, the mosquito-borne Rift Valley Fever Virus (RVFV) is especially concerning as this virus is expanding its territory beyond Africa, causing severe disease in both humans and ruminants. Despite ongoing research, critical gaps remain in understanding the RVFV infection cycle, particularly regarding the initial mechanism of mosquito mediated transmission. Supported by the Marie Skodowska-Curie Actions program, the INTERSECT project will expand knowledge on early RVFV infection in the skin using advanced virus particle analysis and 3D imaging techniques. These insights are crucial for developing targeted therapeutics and improve risk models. The INTERSECT project aims to investigate early RVFV infection in the skin of its natural host, focusing on mosquito transmission and replication. The specific objectives are to 1) map the genomic composition and distribution of RVFV virions, 2) examine the initial infection in ruminant skin, and 3) elucidate the early host immune response. To address its aims, the project will analyze RVFV infected mosquitos, skin biopsies and sera from infected lambs to study RVFV transmission, replication dynamics, and host immune responses. The project will employ cutting-edge methodologies, including tissue optical clearing, fluorescence in situ hybridization (FISH), advanced microscopy, and spatial transcriptomics to uncover critical insights into early RVFV infection mechanisms. The project will provide advanced training in imaging and genomic analysis and enhance transferable skills through publications, presentations, and public engagement. INTERSECT will advance the scientific understanding of RVFV infection and develop methods applicable to other arboviruses, ultimately contributing to global health, informing vaccine development and outbreak prevention.