Genotype II of grass carp reovirus (GCRV), a widespread epidemic virus, poses a significant threat to grass carp farming industry in China. However, the underlying mechanism that different genotype II isolates manifests different degrees of virulence remains unclear. In this work, grass carp were respectively infected with virulent isolate GCRV-HuNan1307 and the avirulent isolate GCRV-GD1108, following by comparative RNA sequencing.