Norovirus major capsid protein VP1 (from genogroups GI.1 and GII.4) (VP1)

The norovirus VP1 protein is the major structural and antigenic protein forming the viral capsid of human norovirus genogroups GI.1 and GII.4, which are the principal causes of epidemic and pandemic viral gastroenteritis worldwide. VP1 consists of a shell (S) domain, providing structural integrity, and a protruding (P) domain (split into P1 and P2 subdomains), which mediates host cell attachment and immunogenicity. The antigenic profiles of GI.1 and GII.4 VP1 differ, with GII.4 exhibiting remarkable antigenic plasticity and frequent emergence of new pandemic strains, while GI.1 (the Norwalk virus) is more antigenically stable. Neutralizing antibodies—naturally acquired, elicited by infection or vaccination—target conformational epitopes within VP1, particularly in the P domain, and block viral interaction with host histo-blood group antigens, which determine susceptibility to infection. VP1-based virus-like particle (VLP) vaccines are in clinical development, showing that raising antibodies to these antigens may protect against infection and mitigate severity. Because VP1 is highly immunogenic, it is both a leading diagnostic marker and a core component of candidate norovirus vaccines.

Other names

Norwalk virus antigen (for GI.1)GII.4 norovirus capsid antigenHuman norovirus capsid proteinNorovirus VLP (virus-like particle, describing recombinant forms)Norovirus shell protein

Vaccine-induced or therapeutic antibodies block VP1’s binding to HBGAs, preventing viral attachment and entry. Neutralizing antibodies may stabilize or disrupt VP1 conformational changes crucial for cell entry. Some antibodies facilitate immune-mediated clearance by targeting exposed or occluded VP1 epitopes.