Finding novel host receptors for Rabies virus

Abstract

The rabies virus (RABV) is an enveloped neurotropic virus and is the causative agent of rabies disease (Fooks et al., 2014). The rabies virion is able to infect the host cell through the endocytic pathway by host cell receptor recognition through its transmembrane glycoprotein which forms a spike on the surface of the virion (Gaudin et al., 1993). To date, five proteinaceous host receptors have been identified: Nicotinic acetylcholine receptor (nAchR) (Lentz et al., 1982), neural cell adhesion molecule 1 (NCAM1) (Thoulouze et al., 1998), neurotrophin receptor p75 (Tuffereau et al., 1998), metabotropic glutamate receptor subtype 2 (mGluR2) (Wang et al., 2018a) and Integrin β-1 (Shua et al., 2020). However, none of these receptors appear to be essential for Rabies infection with viral entry still being observed in receptor knock-out lines. RABV most likely uses a combination of host receptors and other molecules such as carbohydrates, gangliosides and lipids to facilitate viral entry. To better understand Rabies host cell entry, we used co-immunoprecipitation using the Rabies glycoprotein as a bait in combination with liquid chromatography coupled to tandem mass spectrometry. This approach was unable to validate the previously found host receptors, however two potential novel host receptors have been identified in VGF nerve growth factor inducible and γ-enolase.