Unlike other members of the Caliciviridae, which typically encode three open reading frames [6], our analysis and that presented during large scale sequencing of many MNV genomes [32] indicates the presence of a fourth potential ORF in the MNV genome (Figure 1A) In this study we demonstrate that the protein encoded by ORF4 is expressed during virus infection, is not essential for virus replication in tissue culture but plays a role in viral virulence and therefore represents a novel viral virulence factor. The gene discussed is CTTNBP2; the disease is viral infectious disease.