Rabies virus glycoprotein (RABV-G) - Antigenic Site I (RABV-G Site I)

The Rabies virus glycoprotein (RABV-G) is the primary surface protein of the rabies virus, essential for host cell attachment and membrane fusion [6, 11]. Antigenic Site I is a specific epitope on the RABV-G ectodomain, traditionally mapped to residues 263-264 within the Pleckstrin Homology Domain (PHD), though some classifications include residues 226-231 [1, 2, 5]. This site is recognized by neutralizing antibodies that prevent the virus from entering host neurons, thereby halting the progression of the infection [3, 13]. In the context of post-exposure prophylaxis (PEP), Site I is a key target for both polyclonal rabies immunoglobulins and modern monoclonal antibody therapies like Rafivirumab [2, 17]. Antibodies targeting this site typically function by sterically blocking the interaction with host receptors like the nicotinic acetylcholine receptor (nAChR) or by preventing the pH-induced conformational change required for fusion [15, 16]. While Site I is highly conserved among many rabies virus strains, mutations in this region can lead to the emergence of neutralization-resistant variants [1, 10]. Consequently, Site I is often targeted in combination with other antigenic sites in multi-antibody cocktails to ensure broad and robust protection [1, 17]. Monitoring the structural integrity and sequence conservation of Site I is vital for the development of next-generation vaccines and biologics against rabies and related lyssaviruses [1, 5].

Other names

Antigenic Site I of Rabies virus glycoproteinRABV-G Site ISite I of Rabies G proteinEpitope I of Rabies virus glycoprotein

Neutralization of viral infectivity by blocking receptor binding or inhibiting membrane fusion.