Abstract

Rabies virus is a neurotropic virus that replicates and propagates into the nervous system of the infected host. Successful achievement of the virus cycle from the site of entry (usually due to a bite) up to the site of exit (salivary glands) relies on the preservation of the neuronal network. Once the rabies virus has entered the nervous system, its progression is not interrupted by the host defence mechanisms. This virus has evolved sophisticated strategies to (1) disarm premature destruction of the infected neurons and prolong the life span of the infected neurons, (2) evade the innate immune response launched by the infected neurons, and (3) eliminate the protective T cells migrating into the nervous system. In addition, by targeting the nervous system that has the striking capacity to centrally control the immune response, the rabies virus infection benefits also from disarmed host defences. The successful adaptation of the virus to the mammalian nervous system may explain why rabies is fatal in almost all the cases.

Keywords

Rabies virus Neglected diseases Neuroinflammatin Innate immune response IFN PD-L1 B7-H1 Evasive strategies T cells Apoptosis 

References

  1. Babault N et al (2011) Peptides targeting the PDZ domain of PTPN4 are efficient inducers of glioblastoma cell death. Structure 19:1518–1524PubMedGoogle Scholar
  2. Baloul L, Lafon M (2003) Apoptosis and rabies virus neuroinvasion. Biochimie 85:777–788PubMedGoogle Scholar
  3. Baloul L, Camelo S, Lafon M (2004) Up-regulation of Fas ligand (FasL) in the central nervous system: a mechanism of immune evasion by rabies virus. J Neurovirol 10:372–382PubMedGoogle Scholar
  4. Barajon I et al (2009) Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem 57:1013–1023PubMedCentralPubMedGoogle Scholar
  5. Blondel D, Kheddache S, Lahaye X, Dianoux L, Chelbi-Alix MK (2010) Resistance to rabies virus infection conferred by the PMLIV isoform. J Virol 84:10719–10726PubMedCentralPubMedGoogle Scholar
  6. Boivin G, Coulombe Z, Rivest S (2002) Intranasal herpes simplex virus type 2 inoculation causes a profound thymidine kinase dependent cerebral inflammatory response in the mouse hindbrain. Eur J Neurosci 16:29–43PubMedGoogle Scholar
  7. Bottcher T et al (2003) Differential regulation of Toll-like receptor mRNAs in experimental murine central nervous system infections. Neurosci Lett 344:17–20PubMedGoogle Scholar
  8. Brown GC, Neher JJ (2010) Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol 41:242–247PubMedGoogle Scholar
  9. Brzozka K, Finke S, Conzelmann KK (2005) Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3. J Virol 79:7673–7681PubMedCentralPubMedGoogle Scholar
  10. Brzozka K, Finke S, Conzelmann KK (2006) Inhibition of interferon signaling by rabies virus phosphoprotein P: activation-dependent binding of STAT1 and STAT2. J Virol 80:2675–2683PubMedCentralPubMedGoogle Scholar
  11. Bsibsi M, Persoon-Deen C, Verwer RW, Meeuwsen S, Ravid R, Van Noort JM (2006) Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators. Glia 53:688–695PubMedGoogle Scholar
  12. Camelo S, Lafage M, Lafon M (2000) Absence of the p55 Kd TNF-alpha receptor promotes survival in rabies virus acute encephalitis. J Neurovirol 6:507–518PubMedGoogle Scholar
  13. Camelo S, Lafage M, Galelli A, Lafon M (2001) Selective role for the p55 Kd TNF-alpha receptor in immune unresponsiveness induced by an acute viral encephalitis. J Neuroimmunol 113:95–108PubMedGoogle Scholar
  14. Cameron JS et al (2007) Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals. J Neurosci 27:13033–13041PubMedGoogle Scholar
  15. Carosella ED, Moreau P, Aractingi S, Rouas-Freiss N (2001) HLA-G: a shield against inflammatory aggression. Trends Immunol 22:553–555PubMedGoogle Scholar
  16. Charlton KM, Casey GA (1979) Experimental rabies in skunks: immunofluorescence light and electron microscopic studies. Lab Invest 41:36–44PubMedGoogle Scholar
  17. Charlton KM, Casey GA (1981) Experimental rabies in skunks: persistence of virus in denervated muscle at the inoculation site. Can J Comp Med 45:357–362PubMedCentralPubMedGoogle Scholar
  18. Charlton KM, Casey GA, Campbell JB (1984) Experimental rabies in skunks: effects of immunosuppression induced by cyclophosphamide. Can J Comp Med 48:72–77PubMedCentralPubMedGoogle Scholar
  19. Chopy D, Detje CN, Lafage M, Kalinke U, Lafon M (2011a) The type I interferon response bridles rabies virus infection and reduces pathogenicity. J Neurovirol 17:353–367PubMedGoogle Scholar
  20. Chopy D et al (2011b) Ambivalent role of the innate immune response in rabies virus pathogenesis. J Virol 85:6657–6668PubMedCentralPubMedGoogle Scholar
  21. Delhaye S et al (2006) Neurons produce type I interferon during viral encephalitis. Proc Natl Acad Sci USA 103:7835–7840PubMedCentralPubMedGoogle Scholar
  22. Diebold SS et al (2003) Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424:324–328PubMedGoogle Scholar
  23. Dierks RE, Murphy FA, Harrison AK (1969) Extraneural rabies virus infection. Virus development in fox salivary gland. Am J Pathol 54:251–273PubMedCentralPubMedGoogle Scholar
  24. Dong H et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800PubMedGoogle Scholar
  25. Eisenacher K, Steinberg C, Reindl W, Krug A (2007) The role of viral nucleic acid recognition in dendritic cells for innate and adaptive antiviral immunity. Immunobiology 212:701–714PubMedGoogle Scholar
  26. Faul EJ, Wanjalla CN, Suthar MS, Gale M, Wirblich C, Schnell MJ (2010) Rabies virus infection induces type I interferon production in an IPS-1 dependent manner while dendritic cell activation relies on IFNAR signaling. PLoS Pathog 6:e1001016PubMedCentralPubMedGoogle Scholar
  27. Fu ZF et al (1993) Differential effects of rabies and borna disease viruses on immediate-early- and late-response gene expression in brain tissues. J Virol 67:6674–6681PubMedCentralPubMedGoogle Scholar
  28. Galea I, Bechmann I, Perry VH (2007) What is immune privilege (not)? Trends Immunol 28:12–18PubMedGoogle Scholar
  29. Galelli A, Baloul L, Lafon M (2000) Abortive rabies virus central nervous infection is controlled by T lymphocyte local recruitment and induction of apoptosis. J Neurovirol 6:359–372PubMedGoogle Scholar
  30. Goethals S, Ydens E, Timmerman V, Janssens S (2010) Toll-like receptor expression in the peripheral nerve. Glia 58:1701–1709PubMedGoogle Scholar
  31. Gratas C, Tohma Y, Barnas C, Taniere P, Hainaut P, Ohgaki H (1998) Up-regulation of Fas (APO-1/CD95) ligand and down-regulation of Fas expression in human esophageal cancer. Cancer Res 58:2057–2062PubMedGoogle Scholar
  32. Guigoni C, Coulon P (2002) Rabies virus is not cytolytic for rat spinal motoneurons in vitro. J Neurovirol 8:306–317PubMedGoogle Scholar
  33. Hemachudha T, Wacharapluesadee S, Mitrabhakdi E, Wilde H, Morimoto K, Lewis RA (2005) Pathophysiology of human paralytic rabies. J Neurovirol 11:93–100PubMedGoogle Scholar
  34. Hicks DJ, Nunez A, Healy DM, Brookes SM, Johnson N, Fooks AR (2009) Comparative pathological study of the murine brain after experimental infection with classical rabies virus and European bat lyssaviruses. J Comp Pathol 140:113–126PubMedGoogle Scholar
  35. Hirai K et al (1992) Suppression of cell-mediated immunity by street rabies virus infection. Microbiol Immunol 36:1277–1290PubMedGoogle Scholar
  36. Hooper DC, Phares TW, Fabis MJ, Roy A (2009) The production of antibody by invading B cells is required for the clearance of rabies virus from the central nervous system. PLoS Negl Trop Dis 3:e535PubMedCentralPubMedGoogle Scholar
  37. Hornung V et al (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314:994–997PubMedGoogle Scholar
  38. Hunter M et al (2010) Immunovirological correlates in human rabies treated with therapeutic coma. J Med Virol 82:1255–1265PubMedGoogle Scholar
  39. Jackson AC (2014) Rabies: neurology. In: Bentivoglio M, Cavalheiro EA, Kristensson K, Patel N (eds) Neglected tropical diseases and conditions of the nervous system. Springer, New YorkGoogle Scholar
  40. Jackson AC, Randle E, Lawrance G, Rossiter JP (2008) Neuronal apoptosis does not play an important role in human rabies encephalitis. J Neurovirol 14:368–375PubMedGoogle Scholar
  41. Jackson AC, Kammouni W, Zherebitskaya E, Fernyhough P (2010) Role of oxidative stress in rabies virus infection of adult mouse dorsal root ganglion neurons. J Virol 84:4697–4705PubMedCentralPubMedGoogle Scholar
  42. Johnston GR, Webster NR (2009) Cytokines and the immunomodulatory function of the vagus nerve. Br J Anaesth 102:453–462PubMedGoogle Scholar
  43. Juntrakul S, Ruangvejvorachai P, Shuangshoti S, Wacharapluesadee S, Hemachudha T (2005) Mechanisms of escape phenomenon of spinal cord and brainstem in human rabies. BMC Infect Dis 5:104PubMedCentralPubMedGoogle Scholar
  44. Kasempimolporn S, Saengseesom W, Mitmoonpitak C, Akesowan S, Sitprija V (1997) Cell-mediated immunosuppression in mice by street rabies virus not restored by calcium ionophore or PMA. Asian Pac J Allergy Immunol 15:127–132PubMedGoogle Scholar
  45. Kasempimolporn S, Tirawatnapong T, Saengseesom W, Nookhai S, Sitprija V (2001) Immunosuppression in rabies virus infection mediated by lymphocyte apoptosis. Jpn J Infect Dis 54:144–147PubMedGoogle Scholar
  46. Kassis R, Larrous F, Estaquier J, Bourhy H (2004) Lyssavirus matrix protein induces apoptosis by a TRAIL-dependent mechanism involving caspase-8 activation. J Virol 78:6543–6555PubMedCentralPubMedGoogle Scholar
  47. Kim D et al (2007) A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J Biol Chem 282:14975–14983PubMedGoogle Scholar
  48. Klein RS et al (2005) Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis. J Virol 79:11457–11466PubMedCentralPubMedGoogle Scholar
  49. Klingen Y, Conzelmann KK, Finke S (2008) Double-labeled rabies virus: live tracking of enveloped virus transport. J Virol 82:237–245PubMedCentralPubMedGoogle Scholar
  50. Koedel U et al (2004) MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS. Brain 127:1437–1445PubMedGoogle Scholar
  51. Kojima D, Park CH, Satoh Y, Inoue S, Noguchi A, Oyamada T (2009) Pathology of the spinal cord of C57BL/6J mice infected with rabies virus (CVS-11 strain). J Vet Med Sci 71:319–324PubMedGoogle Scholar
  52. Kwidzinski E et al (2003) IDO (indolamine 2,3-dioxygenase) expression and function in the CNS. Adv Exp Med Biol 527:113–118PubMedGoogle Scholar
  53. Lafon M (2005a) Modulation of the immune response in the nervous system by rabies virus. Curr Top Microbiol Immunol 289:239–258PubMedGoogle Scholar
  54. Lafon M (2005b) Rabies virus receptors. J Neurovirol 11:82–87PubMedGoogle Scholar
  55. Lafon M (2008) Immune evasion, a critical strategy for rabies virus. Dev Biol (Basel) 131:413–419Google Scholar
  56. Lafon M (2011) Evasive strategies in rabies virus infection. Adv Virus Res 79:33–53PubMedGoogle Scholar
  57. Lafon M et al (2005) Modulation of HLA-G expression in human neural cells after neurotropic viral infections. J Virol 79:15226–15237PubMedCentralPubMedGoogle Scholar
  58. Lafon M, Megret F, Lafage M, Prehaud C (2006) The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA. J Mol Neurosci 29:185–194PubMedGoogle Scholar
  59. Lafon M et al (2008) Detrimental contribution of the immuno-inhibitor b7-h1 to rabies virus encephalitis. J Immunol 180:7506–7515PubMedGoogle Scholar
  60. Laothamatas J et al (2008) Furious and paralytic rabies of canine origin: neuroimaging with virological and cytokine studies. J Neurovirol 14:119–129PubMedGoogle Scholar
  61. Larrous F, Gholami A, Mouhamad S, Estaquier J, Bourhy H (2010) Two overlapping domains of a lyssavirus matrix protein that acts on different cell death pathways. J Virol 84:9897–9906PubMedCentralPubMedGoogle Scholar
  62. Li XQ, Sarmento L, Fu ZF (2005) Degeneration of neuronal processes after infection with pathogenic, but not attenuated, rabies viruses. J Virol 79:10063–10068PubMedCentralPubMedGoogle Scholar
  63. Liu L et al (2008) Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320:379–381PubMedCentralPubMedGoogle Scholar
  64. Ma Y et al (2006) Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J Cell Biol 175:209–215PubMedCentralPubMedGoogle Scholar
  65. Ma Y, Haynes RL, Sidman RL, Vartanian T (2007) TLR8: an innate immune receptor in brain, neurons and axons. Cell Cycle 6:2859–2868PubMedGoogle Scholar
  66. Masatani T et al (2010) Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response. J Virol 84:4002–4012PubMedCentralPubMedGoogle Scholar
  67. Masatani T et al (2011) Amino acids at positions 273 and 394 in rabies virus nucleoprotein are important for both evasion of host RIG-I-mediated antiviral response and pathogenicity. Virus Res 155(1):168–174PubMedGoogle Scholar
  68. McKimmie CS, Johnson N, Fooks AR, Fazakerley JK (2005) Viruses selectively upregulate Toll-like receptors in the central nervous system. Biochem Biophys Res Commun 336:925–933PubMedGoogle Scholar
  69. Megret F et al (2005) Immunopotentiation of the antibody response against influenza HA with apoptotic bodies generated by rabies virus G-ERA protein-driven apoptosis. Vaccine 23:5342–5350PubMedGoogle Scholar
  70. Megret F et al (2007) Modulation of HLA-G and HLA-E expression in human neuronal cells after rabies virus or herpes virus simplex type 1 infections. Hum Immunol 68:294–302PubMedGoogle Scholar
  71. Menager P et al (2009) Toll-like receptor 3 (TLR3) plays a major role in the formation of rabies virus Negri Bodies. PLoS Pathog 5:e1000315PubMedCentralPubMedGoogle Scholar
  72. Nakamichi K, Inoue S, Takasaki T, Morimoto K, Kurane I (2004) Rabies virus stimulates nitric oxide production and CXC chemokine ligand 10 expression in macrophages through activation of extracellular signal-regulated kinases 1 and 2. J Virol 78:9376–9388PubMedCentralPubMedGoogle Scholar
  73. Nguyen MD, Julien JP, Rivest S (2002) Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 3:216–227PubMedGoogle Scholar
  74. Nuovo GJ, DeFaria DL, Chanona-Vilchi JG, Zhang Y (2005) Molecular detection of rabies encephalitis and correlation with cytokine expression. Mod Pathol 18(1):62–67PubMedGoogle Scholar
  75. Park C et al (2006) TLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expression. Glia 53:248–256PubMedGoogle Scholar
  76. Peltier DC, Simms A, Farmer JR, Miller DJ (2010) Human neuronal cells possess functional cytoplasmic and TLR-mediated innate immune pathways influenced by phosphatidylinositol-3 kinase signaling. J Immunol 184:7010–7021PubMedCentralPubMedGoogle Scholar
  77. Perry LL, Hotchkiss JD, Lodmell DL (1990) Murine susceptibility to street rabies virus is unrelated to induction of host lymphoid depletion. J Immunol 144:3552–3557PubMedGoogle Scholar
  78. Phares TW, Kean RB, Mikheeva T, Hooper DC (2006) Regional differences in blood-brain barrier permeability changes and inflammation in the apathogenic clearance of virus from the central nervous system. J Immunol 176:7666–7675PubMedGoogle Scholar
  79. Phares TW, Stohlman SA, Hinton DR, Atkinson R, Bergmann CC (2010) Enhanced antiviral T cell function in the absence of B7-H1 is insufficient to prevent persistence but exacerbates axonal bystander damage during viral encephalomyelitis. J Immunol 185:5607–5618PubMedCentralPubMedGoogle Scholar
  80. Pichlmair A et al (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314:997–1001PubMedGoogle Scholar
  81. Prehaud C, Megret F, Lafage M, Lafon M (2005) Virus infection switches TLR-3-positive human neurons to become strong producers of beta interferon. J Virol 79:12893–12904PubMedCentralPubMedGoogle Scholar
  82. Prehaud C et al (2010) Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein. Sci Signal 3:ra5PubMedGoogle Scholar
  83. Randall RE, Goodbourn S (2008) Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89:1–47PubMedGoogle Scholar
  84. Rieder M, Conzelmann KK (2009) Rhabdovirus evasion of the interferon system. J Interferon Cytokine Res 29:499–509PubMedGoogle Scholar
  85. Rieder M, Brzozka K, Pfaller CK, Cox JH, Stitz L, Conzelmann KK (2011) Genetic dissection of interferon-antagonistic functions of rabies virus phosphoprotein: inhibition of interferon regulatory factor 3 activation is important for pathogenicity. J Virol 85:842–852PubMedCentralPubMedGoogle Scholar
  86. Rossiter JP, Hsu L, Jackson AC (2009) Selective vulnerability of dorsal root ganglia neurons in experimental rabies after peripheral inoculation of CVS-11 in adult mice. Acta Neuropathol 118:249–259PubMedGoogle Scholar
  87. Rouas-Freiss N, Moreau P, Menier C, Carosella ED (2003) HLA-G in cancer: a way to turn off the immune system. Semin Cancer Biol 13:325–336PubMedGoogle Scholar
  88. Roy A, Hooper DC (2007) Lethal silver-haired bat rabies virus infection can be prevented by opening the blood-brain barrier. J Virol 81:7993–7998PubMedCentralPubMedGoogle Scholar
  89. Roy A, Phares TW, Koprowski H, Hooper DC (2007) Failure to open the blood-brain barrier and deliver immune effectors to central nervous system tissues leads to the lethal outcome of silver-haired bat rabies virus infection. J Virol 81:1110–1118PubMedCentralPubMedGoogle Scholar
  90. Scott CA, Rossiter JP, Andrew RD, Jackson AC (2008) Structural abnormalities in neurons are sufficient to explain the clinical disease and fatal outcome of experimental rabies in yellow fluorescent protein-expressing transgenic mice. J Virol 82:513–521PubMedCentralPubMedGoogle Scholar
  91. Shankar V, Kao M, Hamir AN, Sheng H, Koprowski H, Dietzschold B (1992) Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus. J Virol 66:992–998PubMedCentralPubMedGoogle Scholar
  92. Shimizu K, Ito N, Sugiyama M, Minamoto N (2006) Sensitivity of rabies virus to type I interferon is determined by the phosphoprotein gene. Microbiol Immunol 50:975–978PubMedGoogle Scholar
  93. Sommereyns C, Paul S, Staeheli P, Michiels T (2008) IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog 4:e1000017PubMedCentralPubMedGoogle Scholar
  94. Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296PubMedGoogle Scholar
  95. Sugiura N et al (2011) Gene expression analysis of host innate immune responses in the central nervous system following lethal CVS-11 infection in mice. Jpn J Infect Dis 64:463–472PubMedGoogle Scholar
  96. Tang SC et al (2007) Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci USA 104:13798–13803PubMedCentralPubMedGoogle Scholar
  97. Terrien E et al (2012) Interference with the PTEN-MAST2 interaction by a viral protein leads to cellular relocalization of PTEN. Sci Signal 5:ra58PubMedGoogle Scholar
  98. Thoulouze MI, Lafage M, Montano-Hirose JA, Lafon M (1997) Rabies virus infects mouse and human lymphocytes and induces apoptosis. J Virol 71:7372–7380PubMedCentralPubMedGoogle Scholar
  99. Tobiume M et al (2009) Rabies virus dissemination in neural tissues of autopsy cases due to rabies imported into Japan from the Philippines: immunohistochemistry. Pathol Int 59:555–566PubMedGoogle Scholar
  100. Torres-Anjel MJ, Volz D, Torres MJ, Turk M, Tshikuka JG (1988) Failure to thrive, wasting syndrome, and immunodeficiency in rabies: a hypophyseal/hypothalamic/thymic axis effect of rabies virus. Rev Infect Dis 10(Suppl 4):S710–S725PubMedGoogle Scholar
  101. Tracey KJ (2009) Reflex control of immunity. Nat Rev Immunol 9:418–428PubMedGoogle Scholar
  102. Tshikuka JG, Torres-Anjel MJ, Blenden DC, Elliott SC (1992) The microepidemiology of wasting syndrome, a common link to diarrheal disease, cancer, rabies, animal models of AIDS, and HIV-AIDS YHAIDS). The feline leukemia virus and rabies virus models. Ann N Y Acad Sci 653:274–296PubMedGoogle Scholar
  103. Ugolini G (1995) Specificity of rabies virus as a transneuronal tracer of motor networks: transfer from hypoglossal motoneurons to connected second-order and higher order central nervous system cell groups. J Comp Neurol 356:457–480PubMedGoogle Scholar
  104. Ugolini G (2010) Advances in viral transneuronal tracing. J Neurosci Methods 194(1):2–20, Epub ahead of printPubMedGoogle Scholar
  105. Versteeg GA, Garcia-Sastre A (2010) Viral tricks to grid-lock the type I interferon system. Curr Opin Microbiol 13:508–516PubMedCentralPubMedGoogle Scholar
  106. Vidy A, El Bougrini J, Chelbi-Alix MK, Blondel D (2007) The nucleocytoplasmic rabies virus P protein counteracts interferon signaling by inhibiting both nuclear accumulation and DNA binding of STAT1. J Virol 81:4255–4263PubMedCentralPubMedGoogle Scholar
  107. Vuaillat C et al (2008) High CRMP2 expression in peripheral T lymphocytes is associated with recruitment to the brain during virus-induced neuroinflammation. J Neuroimmunol 193:38–51PubMedGoogle Scholar
  108. Wang ZW et al (2005) Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system. J Virol 79:12554–12565PubMedCentralPubMedGoogle Scholar
  109. Wiktor TJ, Doherty PC, Koprowski H (1977a) In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus. Proc Natl Acad Sci USA 74:334–338PubMedCentralPubMedGoogle Scholar
  110. Wiktor TJ, Doherty PC, Koprowski H (1977b) Suppression of cell-mediated immunity by street rabies virus. J Exp Med 145:1617–1622PubMedGoogle Scholar
  111. Zhang B, Chan YK, Lu B, Diamond MS, Klein RS (2008) CXCR3 mediates region-specific antiviral T cell trafficking within the central nervous system during West Nile virus encephalitis. J Immunol 180:2641–2649PubMedGoogle Scholar
  112. Zhao P et al (2011) Innate immune response gene expression profiles in central nervous system of mice infected with rabies virus. Comp Immunol Microbiol Infect Dis 34(6):503–512PubMedGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Unité de Neuroimmunologie Virale, Département de VirologieInstitut PasteurParisFrance

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