Skip to main content
SpringerLink
Log in

Rabies virus receptors

  • Mini-Review—The Rabies Virus
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind rabies virus and/or facilitate rabies virus entry into cells. Other components of the cell membrane, such as gangliosides, may also participate in the entry of rabies virus. However, little is known of the role of these molecules in vivo. This review proposes a speculative model that accounts for the role of these different molecules in entry and trafficking of rabies virus into the nervous system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bracci L, Antoni G, Cusi MG, Lozzi L, Niccolai N, Petreni S, Rustici M, Santucci A, Soldani P, Valensin PE, et al (1988). Antipeptide monoclonal antibodies inhibit the binding of rabies virus glycoprotein and alpha-bungarotoxin to the nicotinic acetylcholine receptor. Mol Immunol 25: 881–888.

    Article  CAS  PubMed  Google Scholar 

  • Broughan JH, Wunner WH (1995). Characterization of protein involvement in rabies virus binding to BHK-21 cells. Arch Virol 140: 75–93.

    Article  CAS  PubMed  Google Scholar 

  • Burrage TG, Tignor GH, Smith AL (1985). Rabies virus binding at neuromuscular junctions. Virus Res 2: 273–289.

    Article  CAS  PubMed  Google Scholar 

  • Butowt R, von Bartheld CS (2003). Connecting the dots: trafficking of neurotrophins, lectins and diverse pathogens by binding to the neurotrophin receptor p75NTR. Eur J Neurosci 17: 673–680.

    Article  PubMed  Google Scholar 

  • Castellanos JE, Castaneda DR, Velandia AE, Hurtado H (1997). Partial inhibition of the in vitro infection of adult mouse dorsal root ganglion neurons by rabies virus using nicotinic antagonists. Neurosci Lett 229: 198–200.

    Article  CAS  PubMed  Google Scholar 

  • Ceccaldi PE, Gillet JP, Tsiang H (1989). Inhibition of the transport of rabies virus in the central nervous system. J Neuropathol Exp Neurol 48: 620–630.

    Article  CAS  PubMed  Google Scholar 

  • Charlton KM, Nadin-Davis S, Casey GA, Wandeler AI (1997). The long incubation period in rabies: delayed progression of infection in muscle at the site of exposure. Acta Neuropathol (Berl) 94: 73–77.

    Article  CAS  Google Scholar 

  • Copray JC, Jaarsma D, Kust BM, Bruggeman RW, Mantingh I, Brouwer N, Boddeke HW (2003). Expression of the low affinity neurotrophin receptor p75 in spinal motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis. Neuroscience 116: 685–694.

    Article  CAS  PubMed  Google Scholar 

  • Covault J, Sanes JR (1986). Distribution of N-CAM in synaptic and extrasynaptic portions of developing and adult skeletal muscle. J Cell Biol 102: 716–730.

    Article  CAS  PubMed  Google Scholar 

  • Cremer H, Lange R, Christoph A, Plomann M, Vopper G, Roes J, Brown R, Baldwin S, Kraemer P, Scheff S, et al (1994). Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 367: 455–459.

    Article  CAS  PubMed  Google Scholar 

  • Dechant G, Barde YA (2002). The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci 5: 1131–1136.

    Article  CAS  PubMed  Google Scholar 

  • Delling M, Wischmeyer E, Dityatev A, Sytnyk V, Veh RW, Karschin A, Schachner M (2002). The neural cell adhesion molecule regulates cell-surface delivery of G-protein-activated inwardly rectifying potassium channels via lipid rafts. J Neurosci 22: 7154–7164.

    CAS  PubMed  Google Scholar 

  • Dityatev A, Dityateva G, Schachner M (2000). Synaptic strength as a function of post-versus presynaptic expression of the neural cell adhesion molecule NCAM. Neuron 26: 207–217.

    Article  CAS  PubMed  Google Scholar 

  • Dougherty KD, Milner TA (1999). p75NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles. J Comp Neurol 407: 77–91.

    Article  CAS  PubMed  Google Scholar 

  • Etessami R, Conzelmann KK, Fadai-Ghotbi B, Natelson B, Tsiang H, Ceccaldi PE (2000). Spread and pathogenic characteristics of a G-deficient rabies virus recombinant: an in vitro and in vivo study. J Gen Virol 81: 2147–2153.

    CAS  PubMed  Google Scholar 

  • Fertuck HC, Salpeter MM (1974). Localization of acetylcholine receptor by 125I-labeled alpha-bungarotoxin binding at mouse motor endplates. Proc Natl Acad Sci U S A 71: 1376–1378.

    Article  CAS  PubMed  Google Scholar 

  • Gastka M, Horvath J, Lentz TL (1996). Rabies virus binding to the nicotinic acetylcholine receptor alpha subunit demonstrated by virus overlay protein binding assay. J Gen Virol 77: 2437–2440.

    Article  CAS  PubMed  Google Scholar 

  • Gillet JP, Derer P, Tsiang H (1986). Axonal transport of rabies virus in the central nervous system of the rat. J Neuropathol Exp Neurol 45: 619–634.

    Article  CAS  PubMed  Google Scholar 

  • Hanham CA, Zhao F, Tignor GH (1993). Evidence from the anti-idiotypic network that the acetylcholine receptor is a rabies virus receptor. J Virol 67: 530–542.

    CAS  PubMed  Google Scholar 

  • Ito N, Takayama M, Yamada K, Sugiyama M, Minamoto N (2001). Rescue of rabies virus from cloned cDNA and identification of the pathogenicity-related gene: glycoprotein gene is associated with virulence for adult mice. J Virol 75: 9121–9128.

    Article  CAS  PubMed  Google Scholar 

  • Iwasaki Y, Clark HF (1975). Cell to cell transmission of virus in the central nervous system. II. Experimental rabies in mouse. Lab Invest 33: 391–399.

    CAS  PubMed  Google Scholar 

  • Jackson AC, Park H (1999). Experimental rabies virus infection of p75 neurotrophin receptor-deficient mice. Acta Neuropathol (Berl) 98: 641–644.

    Article  CAS  Google Scholar 

  • Kelly RM, StrickPL (2000). Rabies as a transneuronal tracer of circuits in the central nervous system. J Neurosci Methods 103: 63–71.

    Article  CAS  PubMed  Google Scholar 

  • Langevin C, Jaaro H, Bressanelli S, Fainzilber M, Tuffereau C (2002). Rabies virus glycoprotein (RVG) is a trimeric ligand for the N-terminal cysteine-rich domain of the mammalian p75 neurotrophin receptor. J Biol Chem 277: 37655–37662.

    Article  CAS  PubMed  Google Scholar 

  • Langevin C, Tuffereau C (2002). Mutations conferring resistance to neutralization by a soluble form of the neurotrophin receptor (p75NTR) map outside of the known antigenic sites of the rabies virus glycoprotein. J Virol 76: 10756–10765.

    Article  CAS  PubMed  Google Scholar 

  • Lee KF, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R (1992). Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69: 737–749.

    Article  CAS  PubMed  Google Scholar 

  • Lentz TL, Benson RJ, Klimowicz D, Wilson PT, Hawrot E (1986). Binding of rabies virus to purified Torpedo acetylcholine receptor. Brain Res 387: 211–219.

    CAS  PubMed  Google Scholar 

  • Lentz TL, Burrage TG, Smith AL, Crick J, Tignor GH (1982). Is the acetylcholine receptor a rabies virus receptor? Science 215: 182–184.

    Article  CAS  PubMed  Google Scholar 

  • Lentz TL, Hawrot E, Wilson PT (1987). Synthetic peptides corresponding to sequences of snake venom neurotoxins and rabies virus glycoprotein bind to the nicotinic acetylcholine receptor. Proteins 2: 298–307.

    Article  CAS  PubMed  Google Scholar 

  • Lewis P, Fu Y, Lentz TL (2000). Rabies virus entry at the neuromuscular junction in nerve-muscle cocultures. Muscle Nerve 23: 720–730.

    Article  CAS  PubMed  Google Scholar 

  • Lewis P, Lentz TL (1998). Rabies virus entry into cultured rat hippocampal neurons. J Neurocytol 27: 559–573.

    Article  CAS  PubMed  Google Scholar 

  • Mazarakis ND, Azzouz M, Rohll JB, Ellard FM, Wilkes FJ, Olsen AL, Carter EE, Barber RD, Baban DF, Kingsman SM, Kingsman AJ, O’Malley K, Mitrophanous KA (2001). Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery. Hum Mol Genet 10: 2109–2121.

    Article  CAS  PubMed  Google Scholar 

  • Morimoto K, Foley HD, McGettigan JP, Schnell MJ, Dietzschold B (2000). Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach. J NeuroVirol 6: 373–381.

    Article  CAS  PubMed  Google Scholar 

  • Morimoto K, Hooper DC, Carbaugh H, Fu ZF, Koprowski H, Dietzschold B (1998). Rabies virus quasispecies: implications for pathogenesis. Proc Natl Acad Sci U S A 95: 3152–3156.

    Article  CAS  PubMed  Google Scholar 

  • Morimoto K, Hooper DC, Spitsin S, Koprowski H, Dietzschold B (1999). Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures. J Virol 73: 510–518.

    CAS  PubMed  Google Scholar 

  • Murphy FA (1977). Rabies pathogenesis. Arch Virol 54: 279–297.

    Article  CAS  PubMed  Google Scholar 

  • Paratcha G, Ledda F, Ibanez CF (2003). The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 113: 867–879.

    Article  CAS  PubMed  Google Scholar 

  • Pioro EP, Cuello AC (1990a). Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system—I. Forebrain. Neuroscience 34: 57–87.

    CAS  Google Scholar 

  • Pioro EP, Cuello AC (1990b). Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system—II. Brainstem, cerebellum and spinal cord. Neuroscience 34: 89–110.

    Article  CAS  PubMed  Google Scholar 

  • Polo-Parada L, Bose CM, Landmesser LT (2001). Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions. Neuron 32: 815–828.

    Article  CAS  PubMed  Google Scholar 

  • Pugh PC, Corriveau RA, Conroy WG, Berg DK (1995). Novel subpopulation of neuronal acetylcholine receptors among those binding alpha-bungarotoxin. Mol Pharmacol 47: 717–725.

    CAS  PubMed  Google Scholar 

  • Rafuse VF, Polo-Parada L, Landmesser LT (2000). Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice. J Neurosci 20: 6529–6539.

    CAS  PubMed  Google Scholar 

  • Rodriguez-Tebar A, Dechant G, Gotz R, Barde YA (1992). Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J 11: 917–922.

    CAS  PubMed  Google Scholar 

  • Sheard PW, Musaad K, Duxson MJ (2002). Distribution of neurotrophin receptors in the mouse neuromuscular system. Int J Dev Biol 46: 569–575.

    CAS  PubMed  Google Scholar 

  • Superti F, Hauttecoeur B, Morelec MJ, Goldoni P, Bizzini B, Tsiang H (1986). Involvement of gangliosides in rabies virus infection. J Gen Virol 67: 47–56.

    Article  CAS  PubMed  Google Scholar 

  • Superti F, Seganti L, Tsiang H, Orsi N (1984). Role of phospholipids in rhabdovirus attachment to CER cells. Brief report. Arch Virol 81: 321–328.

    Article  CAS  PubMed  Google Scholar 

  • Sytnyk V, Leshchyns’ka I, Delling M, Dityateva G, Dityatev A, Schachner M (2002). Neural cell adhesion molecule promotes accumulation of TGN organelles at sites of neuron-to-neuron contacts. J Cell Biol 159: 649–661.

    Article  CAS  PubMed  Google Scholar 

  • Tang Y, Rampin O, Giuliano F, Ugolini G (1999). Spinal and brain circuits to motoneurons of the bulbospongiosus muscle: retrograde transneuronal tracing with rabies virus. J Comp Neurol 414: 167–192.

    Article  CAS  PubMed  Google Scholar 

  • Thoulouze MI, Lafage M, Schachner M, Hartmann U, Cremer H, Lafon M (1998). The neural cell adhesion molecule is a receptor for rabies virus. J Virol 72: 7181–7190.

    CAS  PubMed  Google Scholar 

  • Tsui-Pierchala BA, Encinas M, Milbrandt J, Johnson EM Jr (2002). Lipid rafts in neuronal signaling and function. Trends Neurosci 25: 412–417.

    Article  CAS  PubMed  Google Scholar 

  • Tuffereau C, Benejean J, Alfonso AM, Flamand A, Fishman MC (1998a). Neuronal cell surface molecules mediate specific binding to rabies virus glycoprotein expressed by a recombinant baculovirus on the surfaces of lepidopteran cells. J Virol 72: 1085–1091.

    CAS  PubMed  Google Scholar 

  • Tuffereau C, Benejean J, Blondel D, Kieffer B, Flamand A (1998b). Low-affinity nerve-growth factor receptor (P75NTR) can serve as a receptor for rabies virus. EMBO J 17: 7250–7259.

    Article  CAS  PubMed  Google Scholar 

  • Tuffereau C, Desmezieres E, Benejean J, Jallet C, Flamand A, Tordo N, Perrin P (2001). Interaction of lyssaviruses with the low-affinity nerve-growth factor receptor p75NTR. J Gen Virol 82: 2861–2867.

    CAS  PubMed  Google Scholar 

  • von Schack D, Casademunt E, Schweigreiter R, Meyer M, Bibel M, Dechant G (2001). Complete ablation of the neurotrophin receptor p75NTR causes defects both in the nervous and the vascular system. Nat Neurosci 4: 977–978.

    Article  Google Scholar 

  • Watson HD, Tignor GH, Smith AL (1981). Entry of rabies virus into the peripheral nerves of mice. J Gen Virol 56: 372–382.

    Article  CAS  PubMed  Google Scholar 

  • Wunner WH, Reagan KJ, Koprowski H (1984). Characterization of saturable binding sites for rabies virus. J Virol 50: 691–697.

    CAS  PubMed  Google Scholar 

  • Yan X, Mohankumar PS, Dietzschold B, Schnell MJ, Fu ZF (2002). The rabies virus glycoprotein determines the distribution of different rabies virus strains in the brain. J NeuroVirol 8: 345–352.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unité de Neuroimmunologie Virale, Département de Neuroscience, Institut Pasteur, 25 rue du Dr Roux, 75724, Paris cedex 15, France

    Monique Lafon

Authors
  1. Monique Lafon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monique Lafon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lafon, M. Rabies virus receptors. Journal of NeuroVirology 11, 82–87 (2005). https://doi.org/10.1080/13550280590900427

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280590900427

Keywords

Search

Navigation