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Rotavirus VP4 is a spike protein located on the outer capsid of the rotavirus virion, playing a fundamental role in viral attachment and infectivity (UniProt: P12473). It is proteolytically cleaved by intestinal trypsin into two fragments, VP8* and VP5*, which are essential for the virus to penetrate host cells (PubMed: 22553325). The VP8* subunit, which defines the P-genotype of the virus, acts as a lectin that binds to specific host cell receptors, including sialic acids and histo-blood group antigens (HBGAs) (PubMed: 24741094). This interaction is a critical determinant of host specificity and susceptibility to different rotavirus strains. As a primary target for the host's neutralizing antibody response, VP4 is a key focus for vaccine development and therapeutic interventions aimed at preventing rotavirus-induced gastroenteritis (PubMed: 29133415). Current vaccines utilize live-attenuated strains to elicit immunity against common VP4 genotypes, while next-generation subunit vaccines often target the VP8* domain specifically (PubMed: 30201725).
Neutralization of viral attachment and entry by blocking the interaction between the VP8* domain and host cell receptors such as histo-blood group antigens (HBGAs) (PubMed: 29133415).
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