For example, the loss of Nsp1 from MHV did not affect replication in tissue culture but severely attenuated the rMHV in vivo[49]; inactivation of the MHV ADP-ribose-1′′phosphatase activity in Nsp3 caused a reduction in virus replication in the livers of infected mice but did not induce liver disease [50] and a single amino acid change in the MHV Nsp14 did not alter the replication of the rMHV in tissue culture but resulted in attenuation in mice [51]. Here, SH2D3A is linked to liver disorder.