Rabies Virus Exploits Cytoskeleton Network to Cause Early Disease Progression and Cellular Dysfunction

Abstract

Rabies virus (RABV) is a cunning neurotropic pathogen and causes top priority neglected tropical diseases in the developing world. The genome of RABV consists of nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA polymerase L protein (L), respectively. The virus causes neuronal dysfunction instead of neuronal cell death by deregulating the polymerization of the actin and microtubule cytoskeleton and subverts the associated binding and motor proteins for efficient viral progression. These binding proteins mainly maintain neuronal structure, morphology, synaptic integrity, and complex neurophysiological pathways. However, much of the exact mechanism of the viral-cytoskeleton interaction is yet unclear because several binding proteins of the actin-microtubule cytoskeleton are involved in multifaceted pathways to influence the retrograde and anterograde axonal transport of RABV. In this review, all the available scientific results regarding cytoskeleton elements and their possible interactions with RABV have been collected through systematic methodology, and thereby interpreted to explain sneaky features of RABV. The aim is to envisage the pathogenesis of RABV to understand further steps of RABV progression inside the cells. RABV interacts in a number of ways with the cell cytoskeleton to produce degenerative changes in the biochemical and neuropathological trails of neurons and other cell types. Briefly, RABV changes the gene expression of essential cytoskeleton related proteins, depolymerizes actin and microtubules, coordinates the synthesis of inclusion bodies, manipulates microtubules and associated motors proteins, and uses actin for clathrin-mediated entry in different cells. Most importantly, the P is the most intricate protein of RABV that performs complex functions. It artfully operates the dynein motor protein along the tracks of microtubules to assist the replication, transcription, and transport of RABV until its egress from the cell. New remedial insights at subcellular levels are needed to counteract the destabilization of the cytoskeleton under RABV infection to stop its life cycle.