Rabies virus glycoprotein (RVG) (RVG)

The Rabies virus glycoprotein (RVG) is the sole protein exposed on the surface of the rabies virus and is the primary determinant of viral neurotropism and pathogenesis (UniProt: P03524). It mediates viral entry by binding to host cell receptors, such as the nicotinic acetylcholine receptor (nAChR), and facilitates membrane fusion within the endosome (PubMed: 16741120). Antigenic site III is a major conformational epitope on the RVG, typically involving residues 330 to 338, and is a critical target for virus-neutralizing antibodies (PubMed: 1711140). In clinical practice, this site is targeted during post-exposure prophylaxis (PEP) using rabies immunoglobulins (RIG) or monoclonal antibodies like Rabivimab to prevent the virus from entering the peripheral nervous system (PubMed: 28838198). Because rabies is almost universally fatal once it reaches the central nervous system, the rapid neutralization of the virus via this epitope is a life-saving intervention. Therapeutic antibodies binding to site III effectively block the virus from interacting with its receptors and inhibit the structural transitions required for infection.

Other names

RABV-GRabies virus G proteinGlycoprotein GAntigenic site IIIRabies virus glycoprotein, antigenic site III conformational epitope

Neutralization of viral infectivity by binding to the antigenic site III of the glycoprotein, which blocks attachment to host receptors (such as nAChR, NCAM, or p75NTR) and prevents the pH-dependent conformational change required for membrane fusion.