A new look at the effect of rabies virus on the nervous system with emphasis on the role of viral glycoprotein

Rabies is caused by the neurotropic rabies virus from the genus Lyssavirus belonging to the Rhabdoviridae family. Despite extensive neurological symptoms including anxiety, rage, hallucinations, depression and hydrophobia, mild pathological alterations are usually seen in the rabies-infected brain. Rabies virus encodes five proteins named N, L, P, M and G. Glycoprotein G forms spikes on the external surface and enables the virus to enter the host cells by connecting and fusing with the cell membrane. The C-terminus amino acid residue of glycoprotein G, called PBM (PDZ binding motif), determines the viral pathogenesity and may manipulate different signaling pathways in the infected neurons. Rabies virus glycoprotein G has been shown to facilitate both short-term and long-term synaptic plasticities, enhances hippocampal-dependent spatial memory performance, and triggers anxious behavior in the infected rats. In this paper, we will review how the rabies virus can alter synaptic function using its glycoprotein G and how it can be used for drug delivery to the central nervous system and for tracing neural networks.