Rotavirus VP8* glycan-binding domain (VP8*)

The Rotavirus VP8* glycan-binding domain is the distal, globular head of the VP4 spike protein, which is essential for the initial stages of rotavirus infection (UniProt P12473). Following proteolytic cleavage of VP4 into VP5* and VP8* by intestinal trypsin, the VP8* domain functions as a viral lectin that recognizes and binds to specific carbohydrate moieties on the surface of host intestinal epithelial cells (Huang et al., 2012). These glycans typically include histo-blood group antigens (HBGAs) such as the Lewis and secretor antigens, which determine the host range and tissue tropism of different rotavirus genotypes (Nordgren et al., 2014). Because this domain is the primary mediator of viral attachment, it is a major target for the development of next-generation subunit vaccines and entry inhibitors. Neutralizing antibodies directed against the VP8* domain can effectively block viral docking, providing a mechanism for protection against rotavirus-induced gastroenteritis (Groome et al., 2020). Current research also explores the use of glycan mimetics, such as human milk oligosaccharides, to competitively inhibit VP8* binding as a therapeutic strategy. This target is particularly significant for addressing the limitations of current live-attenuated vaccines, especially in low-income settings where vaccine efficacy can be reduced.

Other names

VP8* domainVP4 N-terminal fragmentRotavirus attachment proteinVP8* coreVP8* subunit

The VP8* domain mediates the initial attachment of the rotavirus to host cell glycans, specifically histo-blood group antigens (HBGAs). Therapeutic strategies, such as subunit vaccines, aim to elicit neutralizing antibodies that block this binding site, thereby preventing viral entry and subsequent infection (Groome et al., 2020). Investigational glycan mimetics act as decoys to competitively inhibit the interaction between the VP8* domain and host cell receptors.