Viruses of the class Bunyaviricetes are often transmitted by arthropods, including mosquitoes. The innate immune response in mosquitoes comprises several pathways, including sequence-specific degradation through RNA interference (RNAi). It is known that bunyavirus infections are targeted by the innate immune response in mosquitoes and derived cells; however, detailed information is often still missing. In this chapter, we describe a detailed protocol to determine if a protein of interest acts antiviral against bunyavirus infection in mosquito-derived cells. In line, we also describe a detailed protocol to investigate the effect of overexpression of a mosquito-encoded protein or analysis of mutant proteins on bunyavirus infection.