Target intelligence / Profile preview

Rotavirus A VP4 spike protein (VP4)

Target
VP4
Molecular classification
Viral surface protein, Spike protein, Lectin
01

Overview

Rotavirus A VP4 is a surface spike protein that plays a pivotal role in viral infectivity, host cell attachment, and membrane penetration (UniProt P12473). It is biochemically characterized as a protease-sensitive protein that must be cleaved by trypsin-like enzymes into VP5* and VP8* subunits to become active (PubMed: 16439532). The VP8* domain is the primary determinant of the virus's P-genotype (P specificity) and functions as a lectin, binding to specific host cell receptors such as sialic acids or histo-blood group antigens (HBGAs) (PubMed: 22532682). This interaction is a major factor in determining the host range and tissue tropism of different rotavirus strains (PubMed: 24009441). Because VP4 is a major target for neutralizing antibodies, it is a key focus for vaccine design and the development of antiviral agents intended to inhibit the early stages of the viral life cycle (PubMed: 28137898).

Other names
VP4Spike proteinP-genotype determinantProtease-sensitive proteinVP8*VP5*
02

Mechanism of action

Vaccines induce neutralizing antibodies that target the VP4 spike protein, specifically the VP8* domain, to block viral attachment to host cell receptors like histo-blood group antigens (HBGAs), thereby preventing infection (PubMed: 28137898).

03

Biological functions

Viral attachmentCell entryMembrane penetrationHost range determination
04

Disease associations

Rotavirus infectionGastroenteritis
05

Safety considerations

Antigenic drift and shift leading to vaccine escapeStrain replacement in populationsRare risk of intussusception associated with live-attenuated vaccines (PubMed: 25135964)
06

Interacting drugs

Rotarix

3 more in the full profile.

07

Biomarkers

P-genotype (e.g., P[8], P[4])VP4-specific neutralizing antibody titers

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