To analyze the importance of nsP3 MD function for neurovirulence and the induction of innate and adaptive antiviral immune responses in the CNS, we have introduced similar mutations into the nsP3 MD of the TE strain of SINV, a well-characterized mouse model of alphavirus encephalomyelitis that causes fatal disease in 2-week-old mice (5, 52, –, 54). This evidence concerns the gene SH2D3C and encephalomyelitis.