A past report using reassortant viruses between an attenuated MP-12 strain and wt RVFV suggested that RVFV virulence in mouse is under polygenic control [13] . Past studies revealed that the NSs gene, encoded in the S segment, and the NSm gene, encoded in the M segment, both contribute to viral virulence [16, 17, 18] . We presented here our findings that a single nucleotide difference in M847 of the Gn gene of ZH501 substantially affected virulence in mice, a result that further supports the notion that RVFV virulence is under polygenic control [13] .