Journal of NeuroVirology

, Volume 11, Issue 1, pp 82–87 | Cite as

Rabies virus receptors

  • Monique LafonEmail author
Mini-Review—The Rabies Virus


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.


nAChR NCAM p75NTR rabies virus 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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.CrossRefPubMedGoogle Scholar
  2. Broughan JH, Wunner WH (1995). Characterization of protein involvement in rabies virus binding to BHK-21 cells. Arch Virol 140: 75–93.CrossRefPubMedGoogle Scholar
  3. Burrage TG, Tignor GH, Smith AL (1985). Rabies virus binding at neuromuscular junctions. Virus Res 2: 273–289.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. Jackson AC, Park H (1999). Experimental rabies virus infection of p75 neurotrophin receptor-deficient mice. Acta Neuropathol (Berl) 98: 641–644.CrossRefGoogle Scholar
  23. Kelly RM, StrickPL (2000). Rabies as a transneuronal tracer of circuits in the central nervous system. J Neurosci Methods 103: 63–71.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. Lentz TL, Burrage TG, Smith AL, Crick J, Tignor GH (1982). Is the acetylcholine receptor a rabies virus receptor? Science 215: 182–184.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. Lewis P, Fu Y, Lentz TL (2000). Rabies virus entry at the neuromuscular junction in nerve-muscle cocultures. Muscle Nerve 23: 720–730.CrossRefPubMedGoogle Scholar
  31. Lewis P, Lentz TL (1998). Rabies virus entry into cultured rat hippocampal neurons. J Neurocytol 27: 559–573.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. Murphy FA (1977). Rabies pathogenesis. Arch Virol 54: 279–297.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.Google Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. Rafuse VF, Polo-Parada L, Landmesser LT (2000). Structural and functional alterations of neuromuscular junctions in NCAM-deficient mice. J Neurosci 20: 6529–6539.PubMedGoogle Scholar
  43. 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.PubMedGoogle Scholar
  44. Sheard PW, Musaad K, Duxson MJ (2002). Distribution of neurotrophin receptors in the mouse neuromuscular system. Int J Dev Biol 46: 569–575.PubMedGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.CrossRefPubMedGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. Tsui-Pierchala BA, Encinas M, Milbrandt J, Johnson EM Jr (2002). Lipid rafts in neuronal signaling and function. Trends Neurosci 25: 412–417.CrossRefPubMedGoogle Scholar
  51. 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.PubMedGoogle Scholar
  52. 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.CrossRefPubMedGoogle Scholar
  53. 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.PubMedGoogle Scholar
  54. 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.CrossRefGoogle Scholar
  55. Watson HD, Tignor GH, Smith AL (1981). Entry of rabies virus into the peripheral nerves of mice. J Gen Virol 56: 372–382.CrossRefPubMedGoogle Scholar
  56. Wunner WH, Reagan KJ, Koprowski H (1984). Characterization of saturable binding sites for rabies virus. J Virol 50: 691–697.PubMedGoogle Scholar
  57. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2005

Authors and Affiliations

  1. 1.Unité de Neuroimmunologie Virale, Département de NeuroscienceInstitut PasteurParis cedex 15France

Personalised recommendations