Rotavirus Outer Capsid Protein VP4 (VP4) (VP4)

Rotavirus Outer Capsid Protein VP4 is a non-glycosylated spike protein that extends from the surface of the rotavirus particle and plays a critical role in viral infectivity (UniProt P12473). It functions as the primary attachment protein, mediating the initial interaction with host cell receptors such as sialic acids or histo-blood group antigens (HBGAs) through its VP8* subunit (PubMed: 26154548). For the virus to become infectious, VP4 must be proteolytically cleaved by intestinal enzymes like trypsin into two fragments, VP5* and VP8*, which facilitate membrane penetration and cell entry (PubMed: 16439532). As a major determinant of the virus's P-genotype, VP4 is a primary target for neutralizing antibodies induced by natural infection and vaccination (CDC: Rotavirus Vaccination). Current therapeutic strategies primarily involve live-attenuated vaccines, such as Rotarix and RotaTeq, that present VP4 antigens to the immune system to prevent severe gastroenteritis in infants (PubMed: 21844300). Research is also ongoing into the development of VP4-specific nanobodies and small-molecule inhibitors to block the early stages of the viral life cycle (PubMed: 25653450).

Other names

Spike protein VP4P proteinVP4 spikeProtease-cleaved protein VP4

Vaccine-induced neutralizing antibodies bind to the VP4 spikes, particularly the VP8* and VP5* subunits, to block viral attachment to host cell receptors and prevent membrane penetration (PubMed: 26154548).