Human norovirus (HuNoV) is the leading cause of acute gastroenteritis, a disease responsible for an estimated 200,000 deaths per year, mostly in children less than five years old and the elderly. The human norovirus genome is a single-stranded, plus-sensed RNA with 3 open reading frames (ORFs), including an ORF2 major capsid protein (viral protein 1, VP1) composed of shell and protruding (P) domains. Expression of VP1 in insect and mammalian systems leads to self-assembly of 90 VP1 dimers into icosahedral virus-like particles (VLPs) that are antigenically indistinguishable from virions.