Canine distemper virus (CDV) is a Morbillivirus closely related to measles virus, which causes a multisystemic disease in dogs and other carnivore species. CDV infection affects the animal respiratory, gastrointestinal, immune and nervous systems, causing serious illness. CDV is endemic in dogs and wildlife populations worldwide, as commercially available vaccines fail to provide full protection against infection. Researchers have postulated that humans might also be susceptible to CDV. High titers of CDV-specific antibodies have been detected in human blood, and CDV antigen was found in human brain tissues. Recent preliminary data from our lab confirmed that CDV can productively infect several human cell types. Still, the pathogenesis of CDV in humans remains largely unknown. Therefore, the aim of this project is to characterize the key steps of CDV infection in humans. A comparative study will be performed in humans and dogs to highlight possible differences in key steps of CDV neuropathogenesis between species. Specifically, CDV replication kinetics and immune responses will be investigated in relevant human and dog tissues: mucosal explants, peripheral blood monocytic cells and induced pluripotent stem cell (iPSC)-derived neurons. Unravelling CDV pathogenesis will be important to provide prospects for better preventive measures to control CDV emergence in dogs and humans, and better understand the link between Morbillivirus and demyelinating diseases such as MS.