Norovirus is the leading cause of gastroenteritis worldwide, but the mechanism through which norovirus causes disease is currently unknown. Prior research has shown that lymphocyte infection may be key to murine norovirus virulence, but the connection between the two is still unclear. Murine norovirus 1 (MNV-1) is the strain known to have the highest replication efficiency in lymphocytes in vitro as well as the highest virulence in vivo. Key amino acid residues in MNV-1 major capsid protein VP1 were identified, and mutant MNV-1 viruses were created. Replication efficiency of the mutant viruses in B and T cells will be determined as well as virulence of the mutant viruses in vivo. Residue changes that impact both replication efficiency and virulence will elucidate which viral capsid/host cell interactions contribute to norovirus’ ability to elicit disease in hosts.