VP4

VP4 is a structural protein of rotaviruses, non-enveloped double-stranded RNA viruses in the family Reoviridae. It is encoded by genome segment 4 and forms part of the outer capsid, together with the VP7 glycoprotein. In many strains, VP4 is synthesized as a single precursor that is proteolytically cleaved upon maturation by host proteases, such as trypsin, into two subunits, VP8* and VP5*. The VP8* moiety forms the distal spike that engages cell surface receptors, whereas VP5* contributes to membrane penetration during entry. The cleavage enhances infectivity in some host environments, and the conformation of the VP4 spike influences cell tropism and antigenicity.

Genetics and serotyping: The VP4 gene defines the P type of a rotavirus; combined with the VP7-defined G type, it determines the GxP[y] genotype that is used in surveillance. Numerous P-types exist; P[4], P[6], and P[8] are among the most globally encountered. VP4 sequence diversity drives antigenic variation and can affect neutralization by antibodies.

Clinical and research relevance: VP4 is a major target of neutralizing antibodies and is relevant to vaccine design and efficacy. Vaccines against rotavirus induce immune responses against multiple structural proteins including VP4; surveillance of VP4 types helps track circulating strains and inform vaccine composition. Methods for VP4 typing include RT-PCR and sequencing of segment 4.