Rotavirus outer capsid spike protein VP4 (VP4)

Rotavirus outer capsid spike protein VP4 is a structural protein of rotaviruses that forms the protruding spikes on the virion outer surface and serves as the primary cell attachment and entry protein.[1][2][3][4] It is part of the triple-layered capsid and is present as trimers anchored in the outer capsid protein VP7 and the intermediate layer VP6.[1][2] Proteolytic cleavage of VP4 by trypsin or trypsin-like proteases is required for efficient infectivity and produces two noncovalently associated fragments, the N‑terminal VP8* and the larger C‑terminal VP5*.[1][2][3] VP8* mediates initial binding of the virion to host epithelial cell surface glycans and receptors, while VP5* promotes penetration of the host cell membrane and subsequent entry.[1][2][4] VP4 is a major determinant of host range, replication efficiency, diarrheal disease severity, and transmission in animal models, with VP4 gene origin and sequence modulating replication, shedding, and spread between hosts.[1] Structural studies show that VP8* domains from different rotavirus groups adopt distinct folds yet retain glycan-binding functions, highlighting VP4’s role as a glycan-recognizing spike protein for cell entry.[2] As a key surface antigen, VP4 is an important target of neutralizing antibodies and contributes to protective immunity elicited by rotavirus infection and current live attenuated vaccines.[3][4] Note on “P7”: The designation “P7” in “Rotavirus VP4 P7” refers to a **VP4 P genotype** (P) used for rotavirus strain classification, not to a distinct receptor or separate molecular target. VP4 itself is the protein target, and P denotes a specific allelic/genotypic form of VP4.

Other names

Rotavirus VP4Outer capsid protein VP4Rotavirus spike protein VP4Rotavirus attachment protein VP4VP4 spike proteinRotavirus cell attachment protein VP4

Neutralizing antibodies bind VP4 or its cleaved domains (VP8* and/or VP5*) to block virion attachment to host cell receptors and/or membrane penetration, thereby preventing rotavirus entry and infection[1][2][4]