GENETICALLY-DETERMINED RESISTANCE TO FLAVIVIRUS INFECTION IN WILD MUS-MUSCULUS-DOMESTICUS AND OTHER TAXONOMIC GROUPS IN THE GENUS MUS

Inherited resistance to flaviviruses in laboratory mice is a rare trai t conferred by an autosomal dominant gene (Flv(r)). To provide informa tion on genetic resistance to flaviviruses in wild mice, we analysed ( i) wild M. m. domesticus trapped in Australia, and (ii) mice represent ing other species and subspecies in the genus Mus. Mice were screened for resistance relative to C3H/HeJ mice by intracerebral challenge wit h Murray Valley encephalitis virus or yellow fever virus, and breeding studies were undertaken to identify inherited resistance factors. Wid espread flavivirus resistance was demonstrated in Australian M. m. dom esticus. A single, autosomal dominant Flv(r)-like gene appeared to be primarily responsible, but there was some evidence for additional inhe rited resistance factors. Flavivirus resistance was also identified in other taxonomic groups, and a genetic basis for this resistance was d emonstrated in M. m. musculus (Skive), M. spretus, and M. spicilegus. Interestingly, M. m. musculus (CZI-O) were more susceptible than C3H/H eJ mice. Our findings show that genetic resistance to flaviviruses is common in divergent taxonomic groups in the genus Mus, suggesting that the trait has an ancient evolutionary origin, but whether flavivirus resistance genes have an anti-viral role or serve some other function is unknown.