Protocol for establishing a murine Toscana virus infection model and downstream cellular analysis of skin tissue and cells.

Here, we present an in vivo approach to study virus-vector-host interactions during Toscana virus (TOSV) infection in mouse skin. We describe preparation of viral stocks and subcutaneous TOSV inoculation into dorsal upper foot skin, either alone, with sand-fly salivary gland extract (SGE), or following sand-fly biting. We then detail tissue collection and generation of single-cell suspensions. Finally, we describe flow cytometric detection of infected cells, magnetic isolation of dermal fibroblasts, and RNA extraction for transcriptomic analysis. For complete details on the use and execution of this protocol, please refer to Keskek Turk et al.1.