Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The spread and evolution of rabies virus: conquering new frontiers

Key Points

  • With much of the molecular virology characterized, we are now gaining an appreciation of how nuanced rabies virus infection dynamics are and how immune status relates to transmission.

  • The growing number of recognized rabies virus-related lyssaviruses highlights shortcomings in our discriminatory diagnostics and raises questions about their impact on human health. The lack of therapeutics for some of these lyssaviruses is a major concern.

  • Enzootic maintenance of rabies virus within a population depends on transmission within narrow windows. The virus avoids extinction by both general and reservoir host-specific mechanisms with remarkable epidemiological plasticity.

  • Features of rabies virus biology, ecology and evolution have made the virus a model pathogen for disease ecology and evolution. Recent work using mathematical models and phylodynamic analyses have enabled reconstruction and forecasting of epizootic spread of the virus at the landscape level.

  • At an evolutionary level, there is evidence that strong barriers prevent rabies virus from establishing in new host species, and both ecological opportunities and viral adaptation are needed to overcome these barriers. Studies of rabies virus molecular evolutionary dynamics have revealed the role of purifying selection and the importance of viral and host genetic backgrounds in host shifts. Further study of contemporary host shifts will likely shed light on the unknown origin of rabies.

  • We suggest that efforts be focused on developing strategies and technologies to manage rabies viruses within bat reservoirs as previously done with carnivores, integrating diagnostics that can rapidly differentiate strains into surveillance efforts, honing our predictive power to detect outbreaks and coordinating local resources to halt the spread of this lethal zoonosis.

Abstract

Rabies is a lethal zoonotic disease that is caused by lyssaviruses, most often rabies virus. Despite control efforts, sporadic outbreaks in wildlife populations are largely unpredictable, underscoring our incomplete knowledge of what governs viral transmission and spread in reservoir hosts. Furthermore, the evolutionary history of rabies virus and related lyssaviruses remains largely unclear. Robust surveillance efforts combined with diagnostics and disease modelling are now providing insights into the epidemiology and evolution of rabies virus. The immune status of the host, the nature of exposure and strain differences all clearly influence infection and transmission dynamics. In this Review, we focus on rabies virus infections in the wildlife and synthesize current knowledge in the rapidly advancing fields of rabies virus epidemiology and evolution, and advocate for multidisciplinary approaches to advance our understanding of this disease.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The rabies virus life cycle and cell entry.
Figure 2: Lyssavirus transmission dynamics in bats and terrestrial animals.
Figure 3: Current continental distribution of bat lyssaviruses and terrestrial mammalian lyssavirus reservoirs.
Figure 4: The influence of reservoir host ecology on the epidemiology of rabies.

References

  1. 1

    Baer, G. M. The Natural History of Rabies. (CRC Press, 1991).

    Google Scholar 

  2. 2

    Yuhong, W. Rabies and rabid dogs in Sumerian and Akkadian literature. J. Am. Oriental Soc. 121, 32–43 (2001).

    Google Scholar 

  3. 3

    Tarantola, A. Four thousand years of concepts relating to rabies in animals and humans, its prevention and its cure. Trop. Med. Infect. Dis. 2, 5 (2017).

    PubMed Central  Google Scholar 

  4. 4

    Baer, G. M. in Rabies 2nd edn (eds Wunner, W. H. & Jackson, A. C.) 1–22 (Academic Press, 2007).

    Google Scholar 

  5. 5

    Belotto, A., Leanes, L., Schneider, M., Tamayo, H. & Correa, E. Overview of rabies in the Americas. Virus Res. 111, 5–12 (2005).

    CAS  PubMed  Google Scholar 

  6. 6

    Ribadeau-Dumas, F. et al. Travel-associated rabies in pets and residual rabies risk, Western Europe. Emerg. Infect. Dis. 22, 1268–1271 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Biek, R., Henderson, J. C., Waller, L. A., Rupprecht, C. E. & Real, L. A. A high-resolution genetic signature of demographic and spatial expansion in epizootic rabies virus. Proc. Natl Acad. Sci. USA 104, 7993–7998 (2007). This study establishes RABV as a model for viral phylodynamics, demonstrating that the dynamics of viral invasions can be estimated to high resolution from spatially and temporally annotated viral sequences.

    CAS  PubMed  Google Scholar 

  8. 8

    Kuzmina, N. A. et al. The phylogeography and spatiotemporal spread of south-central skunk rabies virus. PLoS ONE 8, e82348 (2013).

    PubMed  PubMed Central  Google Scholar 

  9. 9

    Martinez-Burnes, J. et al. An outbreak of vampire bat-transmitted rabies in cattle in northeastern Mexico. Can. Vet. J. 38, 175–177 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Benavides, J. A., Valderrama, W. & Streicker, D. G. Spatial expansions and travelling waves of rabies in vampire bats. Proc. R. Soc. Lond. B Biol Sci. https://doi.org/10.1098/rspb.2016.0328 (2016).

    Google Scholar 

  11. 11

    Birhane, M. G. et al. Rabies surveillance in the United States during 2015. J. Am. Vet. Med. Assoc. 250, 1117–1130 (2017).

    PubMed  Google Scholar 

  12. 12

    Favoretto, S. R., de Mattos, C. C., Morais, N. B., Araujo, F. A. A. & de Mattos, C. A. Rabies in marmosets (Callithrix jacchus), Ceara, Brazil. Emerg. Infect. Dis. 7, 1062–1065 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Castillo-Neyra, R. et al. Barriers to dog rabies vaccination during an urban rabies outbreak: qualitative findings from Arequipa, Peru. PLoS Negl. Trop. Dis. 11, e0005460 (2017).

    PubMed  PubMed Central  Google Scholar 

  14. 14

    Banyard, A. C., Evans, J. S., Luo, T. R. & Fooks, A. R. Lyssaviruses and bats: emergence and zoonotic threat. Viruses 6, 2974–2990 (2014). This review reports on the detection, transmission and maintenance of rabies-related lyssaviruses in bats.

    PubMed  PubMed Central  Google Scholar 

  15. 15

    [No authors listed.] Human rabies: 2016 updates and call for data. Wkly Epidemiol. Rec. 92, 77–88 (2017).

  16. 16

    Hampson, K. et al. Estimating the global burden of endemic canine rabies. PLoS Negl. Trop. Dis. 9, e0003709 (2015).

    PubMed  PubMed Central  Google Scholar 

  17. 17

    Badrane, H., Bahloul, C., Perrin, P. & Tordo, N. Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity. J. Virol. 75, 3268–3276 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Ceballos, N. A. et al. Novel lyssavirus in bat, Spain. Emerg. Infect. Dis. 19, 793 (2013).

    PubMed Central  Google Scholar 

  19. 19

    Gunawardena, P. S. et al. Lyssavirus in Indian Flying Foxes, Sri Lanka. Emerg. Infect. Dis. 22, 1456 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Coertse, J. et al. New isolations of the rabies-related Mokola virus from South Africa. BMC Veterinary Res. 13, 37 (2017).

    Google Scholar 

  21. 21

    Marston, D. A. et al. Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet. Emerg. Infect. Dis. 18, 664–667 (2012).

    PubMed  PubMed Central  Google Scholar 

  22. 22

    Evans, J. S., Horton, D. L., Easton, A. J., Fooks, A. R. & Banyard, A. C. Rabies virus vaccines: is there a need for a pan-lyssavirus vaccine? Vaccine 30, 7447–7454 (2012).

    CAS  PubMed  Google Scholar 

  23. 23

    Mebatsion, T., Cox, J. H. & Frost, J. W. Isolation and characterization of 115 street rabies virus isolates from Ethiopia by using monoclonal antibodies: identification of 2 isolates as Mokola and Lagos bat viruses. J. Infect. Dis. 166, 972–977 (1992). This study focuses on the prevalence of phylogroup II lyssaviruses in terrestrial mammals.

    CAS  PubMed  Google Scholar 

  24. 24

    Mallewa, M. et al. Rabies encephalitis in malaria-endemic area, Malawi, Africa. Emerg. Infect. Dis. 13, 136–139 (2007).

    PubMed  PubMed Central  Google Scholar 

  25. 25

    Hanlon, C. A. et al. Efficacy of rabies biologics against new lyssaviruses from Eurasia. Virus Res. 111, 44–54 (2005).

    CAS  PubMed  Google Scholar 

  26. 26

    Liu, Y. et al. Evaluation of rabies biologics against Irkut virus isolated in China. J. Clin. Microbiol. 51, 3499–3504 (2013).

    PubMed  PubMed Central  Google Scholar 

  27. 27

    De Benedictis, P. et al. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. EMBO Mol. Med. 8, 407–421 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Conzelmann, K. K., Cox, J. H., Schneider, L. G. & Thiel, H. J. Molecular cloning and complete nucleotide sequence of the attenuated rabies virus SAD B19. Virology 175, 485–499 (1990).

    CAS  PubMed  Google Scholar 

  29. 29

    Tordo, N., Poch, O., Ermine, A., Keith, G. & Rougeon, F. Walking along the rabies genome: is the large G-L intergenic region a remnant gene? Proc. Natl Acad. Sci. USA 83, 3914–3918 (1986). This is the first study to report a complete RABV genome sequence.

    CAS  PubMed  Google Scholar 

  30. 30

    Ge, P. et al. Cryo-EM model of the bullet-shaped vesicular stomatitis virus. Science 327, 689–693 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Cureton, D. K., Massol, R. H., Saffarian, S., Kirchhausen, T. L. & Whelan, S. P. Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog. 5, e1000394 (2009).

    PubMed  PubMed Central  Google Scholar 

  32. 32

    Jackson, A. C. in Rabies 2nd edn (eds Wunner, W. H. & Jackson, A. C.) 341–372 (Academic Press, 2007).

    Google Scholar 

  33. 33

    Rossiter, J. P. & Jackson, A. C. in Rabies 2nd edn (eds Wunner, W. H. & Jackson, A. C.) 383–403 (Academic Press, 2007).

    Google Scholar 

  34. 34

    Schnell, M. J., McGettigan, J. P., Wirblich, C. & Papaneri, A. The cell biology of rabies virus: using stealth to reach the brain. Nat. Rev. Microbiol. 8, 51–61 (2010).

    CAS  PubMed  Google Scholar 

  35. 35

    Dietzschold, B., Li, J., Faber, M. & Schnell, M. Concepts in the pathogenesis of rabies. Future Virol. 3, 481–490 (2008). This work provides an overview of viral factors that affect the pathogenicity of RABV.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Lafon, M. Rabies virus receptors. J. Neurovirol. 11, 82–87 (2005).

    CAS  PubMed  Google Scholar 

  37. 37

    Piccinotti, S. & Whelan, S. P. Rabies internalizes into primary peripheral neurons via clathrin coated pits and requires fusion at the cell body. PLoS Pathog. 12, e1005753 (2016).

    PubMed  PubMed Central  Google Scholar 

  38. 38

    Xu, H. et al. Real-time imaging of rabies virus entry into living vero cells. Sci. Rep. 5, 11753 (2015).

    PubMed  PubMed Central  Google Scholar 

  39. 39

    Davis, B. D., Rall, G. F. & Schnell, M. J. Everything you always wanted to know about rabies virus (but were afraid to ask). Annu. Rev. Virol. 2, 451–471 (2015). This work is a comprehensive review of RABV and RABV infection.

    CAS  PubMed  Google Scholar 

  40. 40

    Yamaoka, S. et al. Involvement of the rabies virus phosphoprotein gene in neuroinvasiveness. J. Virol. 87, 12327–12338 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Velandia-Romero, M. L., Castellanos, J. E. & Martínez-Gutiérrez, M. In vivo differential susceptibility of sensory neurons to rabies virus infection. J. Neurovirol. 19, 367–375 (2013).

    Google Scholar 

  42. 42

    Jackson, A. C. et al. Extraneural organ involvement in human rabies. Lab. Invest. 79, 945–951 (1999).

    CAS  PubMed  Google Scholar 

  43. 43

    de Souza, A. & Madhusudana, S. N. Survival from rabies encephalitis. J. Neurol. Sci. 339, 8–14 (2014).

    PubMed  Google Scholar 

  44. 44

    Wunner, W. H. & Jackson, A. C. Rabies: Scientific Basis of the Disease and its Management 3rd edn (Academic Press, 2013).

    Google Scholar 

  45. 45

    Hanlon, C. A., Niezgoda, M. & Rupprecht, C. E. in Rabies 2nd edn (eds Wunner, W. H. & Jackson, A. C.) 201–258 (Academic Press, 2007).

    Google Scholar 

  46. 46

    Hemachudha, T. et al. Immunologic study of human encephalitic and paralytic rabies: preliminary report of 16 patients. Am. J. Med. 84, 673–677 (1988).

    CAS  PubMed  Google Scholar 

  47. 47

    Shuangshoti, S. et al. Intracellular spread of rabies virus is reduced in the paralytic form of canine rabies compared to the furious form. PLoS Negl. Trop. Dis. 10, e0004748 (2016).

    PubMed  PubMed Central  Google Scholar 

  48. 48

    Hemachudha, T. et al. Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurol. 12, 498–513 (2013).

    PubMed  Google Scholar 

  49. 49

    Katz, I. S. S. et al. Delayed progression of rabies transmitted by a vampire bat. Arch. Virol. 161, 2561–2566 (2016).

    CAS  PubMed  Google Scholar 

  50. 50

    Mesquita, L. P. et al. A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant. Arch. Virol. 162, 3671–3679 (2017).

    CAS  PubMed  Google Scholar 

  51. 51

    Begeman, L. et al. Comparative pathogenesis of rabies in bats and carnivores, and implications for spillover to humans. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(17)30574-1 (2017).

    PubMed  Google Scholar 

  52. 52

    Jackson, F. R. et al. Experimental rabies virus infection of big brown bats (Eptesicus fuscus). J. Wildl. Dis. 44, 612–621 (2008).

    CAS  PubMed  Google Scholar 

  53. 53

    Obregón-Morales, C. et al. Experimental infection of Artibeus intermedius with a vampire bat rabies virus. Comp. Immunol. Microbiol. Infect. Dis. 52, 43–47 (2017).

    PubMed  Google Scholar 

  54. 54

    Turmelle, A. S. et al. Response to vaccination with a commercial inactivated rabies vaccine in a captive colony of Brazilian free-tailed bats (Tadarida brasiliensis). J. Zoo Wildl. Med. 41, 140–143 (2010).

    PubMed  Google Scholar 

  55. 55

    Baker, M., Schountz, T. & Wang, L. F. Antiviral immune responses of bats: a review. Zoonoses Publ. Health 60, 104–116 (2013).

    CAS  Google Scholar 

  56. 56

    Messenger, S. L., Smith, J. S., Orciari, L. A., Yager, P. A. & Rupprecht, C. E. Emerging pattern of rabies deaths and increased viral infectivity. Emerg. Infect. Dis. 9, 151–154 (2003).

    PubMed  PubMed Central  Google Scholar 

  57. 57

    Constantine, D. G., Emmons, R. W. & Woodie, J. D. Rabies virus in nasal mucosa of naturally infected bats. Science 175, 1255–1256 (1972).

    CAS  PubMed  Google Scholar 

  58. 58

    Lafon, M. in Rabies 2nd edn (eds Wunner, W. H. & Jackson, A. C.) 489–504 (Academic Press, 2007).

    Google Scholar 

  59. 59

    Brzózka, K., Finke, S. & Conzelmann, K.-K. Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3. J. Virol. 79, 7673–7681 (2005).

    PubMed  PubMed Central  Google Scholar 

  60. 60

    Yang, J., Koprowski, H., Dietzschold, B. & Fu, Z. F. Phosphorylation of rabies virus nucleoprotein regulates viral RNA transcription and replication by modulating leader RNA encapsidation. J. Virol. 73, 1661–1664 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Scott, T. P. & Nel, L. H. Subversion of the immune response by rabies virus. Viruses 8, 231 (2016).

    PubMed Central  Google Scholar 

  62. 62

    Rieder, M. & Conzelmann, K.-K. Interferon in rabies virus infection. Adv. Virus Res. 79, 91 (2011). This review covers the interplay between the innate immune response and the strategies of RABV to antagonize it.

    CAS  PubMed  Google Scholar 

  63. 63

    Johnson, N., Cunningham, A. F. & Fooks, A. R. The immune response to rabies virus infection and vaccination. Vaccine 28, 3896–3901 (2010).

    CAS  PubMed  Google Scholar 

  64. 64

    Moore, S. M. & Hanlon, C. A. Rabies-specific antibodies: measuring surrogates of protection against a fatal disease. PLoS Negl. Trop. Dis. 4, e595 (2010).

    PubMed  PubMed Central  Google Scholar 

  65. 65

    Hooper, D. C., Phares, T. W., Fabis, M. J. & Roy, A. 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, e535 (2009).

    PubMed  PubMed Central  Google Scholar 

  66. 66

    Smith, J., Yager, P. & Baer, G. in Laboratory Techniques in Rabies (eds Meslin, F. X., Kaplan, M. M. & Koprowski, H.) 181–192 (World Health Organization, 1996).

    Google Scholar 

  67. 67

    De Thoisy, B. et al. Bioecological drivers of rabies virus circulation in a Neotropical bat community. PLoS Negl. Trop. Dis. 10, e0004378 (2016).

    PubMed  PubMed Central  Google Scholar 

  68. 68

    Streicker, D. G., Franka, R., Jackson, F. R. & Rupprecht, C. E. Anthropogenic roost switching and rabies virus dynamics in house-roosting big brown bats. Vector Borne Zoonot. Dis. 13, 498–504 (2013).

    Google Scholar 

  69. 69

    Turmelle, A. S. et al. Ecology of rabies virus exposure in colonies of Brazilian free-tailed Bats (Tadarida brasiliensis) at natural and man-made roosts in Texas. Vector Borne Zoonot. Dis. 10, 165–175 (2010).

    Google Scholar 

  70. 70

    Everard, C. & Everard, J. Mongoose rabies in the Caribbean. Ann. NY Acad. Sci. 653, 356–366 (1992).

    CAS  PubMed  Google Scholar 

  71. 71

    Gilbert, A. et al. Antibody response of cattle to vaccination with commercial modified live rabies vaccines in Guatemala. Prev. Vet. Med. 118, 36–44 (2015).

    PubMed  Google Scholar 

  72. 72

    Gilbert, A. T. et al. Evidence of rabies virus exposure among humans in the Peruvian Amazon. Am. J. Trop. Med. Hyg. 87, 206–215 (2012).

    PubMed  PubMed Central  Google Scholar 

  73. 73

    Ramsden, R. O. & Johnston, D. H. Studies on the oral infectivity of rabies virus in carnivora. J. Wildl. Dis. 11, 318–324 (1975).

    CAS  PubMed  Google Scholar 

  74. 74

    Bell, J. F. & Moore, G. J. Susceptibility of carnivora to rabies virus administered orally. Am. J. Epidemiol. 93, 176–182 (1971).

    CAS  PubMed  Google Scholar 

  75. 75

    Charlton, K. & Casey, G. Experimental rabies in skunks: oral, nasal, tracheal and intestinal exposure. Can. J. Comp. Med. 43, 168–172 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Winkler, W. G., Fashinell, T. R., Leffingwell, L., Howard, P. & Conomy, J. P. Airborne rabies transmission in a laboratory worker. JAMA 226, 1219–1221 (1973).

    CAS  PubMed  Google Scholar 

  77. 77

    Gibbons, R. V. Cryptogenic rabies, bats, and the question of aerosol transmission. Ann. Emerg. Med. 39, 528–536 (2002).

    PubMed  Google Scholar 

  78. 78

    Srinivasan, A. et al. Transmission of rabies virus from an organ donor to four transplant recipients. N. Engl. J. Med. 352, 1103–1111 (2005).

    CAS  PubMed  Google Scholar 

  79. 79

    Hellenbrand, W., Meyer, C., Rasch, G., Steffens, I. & Ammon, A. Cases of rabies in Germany following organtransplantation. EuroSurveillance 10, E050224–050226 (2004).

    Google Scholar 

  80. 80

    Preuss, M. A. et al. Intravenous inoculation of a bat-associated rabies virus causes lethal encephalopathy in mice through invasion of the brain via neurosecretory hypothalamic fibers. PLoS Pathog. 5, e1000485 (2009). This study provides evidence that bat-derived RABV spreads differently than classic RABV.

    PubMed  PubMed Central  Google Scholar 

  81. 81

    Morimoto, K. et al. Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America. Proc. Natl Acad. Sci. USA 93, 5653–5658 (1996).

    CAS  PubMed  Google Scholar 

  82. 82

    Jackson, A. C. Current and future approaches to the therapy of human rabies. Antiviral Res. 99, 61–67 (2013).

    CAS  PubMed  Google Scholar 

  83. 83

    Keeling, M. J. & Rohani, P. Modeling Infectious Diseases in Humans and Animals (Princeton Univ. Press, 2008).

    Google Scholar 

  84. 84

    Hampson, K. et al. Transmission dynamics and prospects for the elimination of canine rabies. PLoS Biol. 7, e1000053 (2009). By estimating the first field-derived estimates of the basic reproductive number of dog RABV from contact tracing and mathematical models, this study shows that rabies might be eliminated through sustained dog vaccination programmes.

    PubMed Central  Google Scholar 

  85. 85

    Blackwood, J. C., Streicker, D. G., Altizer, S. & Rohani, P. Resolving the roles of immunity, pathogenesis, and immigration for rabies persistence in vampire bats. Proc. Natl Acad. Sci. USA 110, 20837–20842 (2013). This study combines longitudinal field studies with mathematical models to show that the long-term maintenance of rabies in vampire bats relies on spatial dynamics and immunizing abortive infections.

    CAS  PubMed  Google Scholar 

  86. 86

    Anderson, R. M., Jackson, H. C., May, R. M. & Smith, A. M. Population dynamics of fox rabies in Europe. Nature 289, 765–771 (1981).

    CAS  PubMed  Google Scholar 

  87. 87

    Childs, J. E. et al. Predicting the local dynamics of epizootic rabies among raccoons in the United States. Proc. Natl Acad. Sci. USA 97, 13666–13671 (2000).

    CAS  PubMed  Google Scholar 

  88. 88

    Courtin, F., Carpenter, T. E., Paskin, R. D. & Chomel, B. B. Temporal patterns of domestic and wildlife rabies in central Namibia stock-ranching area, 1986–1996. Prev. Vet. Med. 43, 13–28 (2000).

    CAS  PubMed  Google Scholar 

  89. 89

    Coleman, P. G. & Dye, C. Immunization coverage required to prevent outbreaks of dog rabies. Vaccine 14, 185–186 (1996).

    CAS  PubMed  Google Scholar 

  90. 90

    Streicker, D. G. et al. Ecological and anthropogenic drivers of rabies exposure in vampire bats: implications for transmission and control. Proc. R. Soc. Lond. B Biol Sci. 279, 3384–3392 (2012). This study provides the first evidence that culling vampire bats may be ineffective to eliminate RABV.

    Google Scholar 

  91. 91

    Morters, M. K. et al. Evidence-based control of canine rabies: a critical review of population density reduction. J. Animal Ecol. 82, 6–14 (2013). This review assesses the evidence for various mechanisms through which animal culls are hypothesized to be an effective strategy for the control of RABV and concludes that vaccination should be the preferred strategy.

    Google Scholar 

  92. 92

    Lloyd-Smith, J. O., Schreiber, S. J., Kopp, P. E. & Getz, W. M. Superspreading and the effect of individual variation on disease emergence. Nature 438, 355–359 (2005).

    CAS  PubMed  Google Scholar 

  93. 93

    Davis, A. D., Dupuis, M. & Rudd, R. J. Extended incubation period of rabies virus in a captive big brown bat (Eptesicus fuscus). J. Wildl. Dis. 48, 508–511 (2012). This study provides evidence for long incubation times when bat-derived RABV infects its natural host (bats).

    PubMed  Google Scholar 

  94. 94

    Moore, G. J. & Raymond, G. H. Prolonged incubation period of rabies in a naturally infected insectivorous bat, Eptesicus foscus (beauvois). J. Wildl. Dis. 6, 167–168 (1970).

    CAS  PubMed  Google Scholar 

  95. 95

    Smith, J. S., Fishbein, D. B., Rupprecht, C. E. & Clark, K. Unexplained Rabies in Three Immigrants in the United States a Virologic Investigation. N. Engl. J. Med. 324, 205–211 (1991).

    CAS  PubMed  Google Scholar 

  96. 96

    Beyer, H. L. et al. Metapopulation dynamics of rabies and the efficacy of vaccination. Proc. R. Soc. Lond. B Biol Sci. 278, 2182–2190 (2011).

    Google Scholar 

  97. 97

    George, D. B. et al. Host and viral ecology determine bat rabies seasonality and maintenance. Proc. Natl Acad. Sci. USA 108, 10208–10213 (2011). This study uses mathematical models and field studies to show that the observed seasonal dynamics of RABV in temperate bats may be achieved through long incubation periods during hibernation and birth pulses.

    CAS  PubMed  Google Scholar 

  98. 98

    Davis, A. D. et al. Overwintering of rabies virus in silver haired bats (Lasionycteris noctivagans). PLoS ONE 11, e0155542 (2016).

    PubMed  PubMed Central  Google Scholar 

  99. 99

    Streicker, D. G., Lemey, P., Velasco-Villa, A. & Rupprecht, C. E. Rates of viral evolution are linked to host geography in bat rabies. PLoS Pathog. 8, e1002720 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100

    Steece, R. R. & Altenbach, J. S. J. S. Prevalence of rabies specific antibodies in the Mexican free-tailed bat (Tadarida brasiliensis mexicana) at Lava Cave, New Mexico. J. Wildl. Dis. 25, 490–496 (1989).

    CAS  PubMed  Google Scholar 

  101. 101

    Amengual, B., Bourhy, H., López-Roíg, M. & Serra-Cobo, J. Temporal dynamics of European bat lyssavirus type 1 and survival of Myotis myotis bats in natural colonies. PLoS ONE 2, e566 (2007).

    PubMed  PubMed Central  Google Scholar 

  102. 102

    Fooks, A. R., Brookes, S. M., Johnson, N., McElhinney, L. M. & Hutson, A. M. European bat lyssaviruses: an emerging zoonosis. Epidemiol. Infect. 131, 1029–1039 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103

    Franka, R. et al. Susceptibility of North American big brown bats (Eptesicus fuscus) to infection with European bat lyssavirus type 1. J. Gen. Virol. 89, 1998–2010 (2008).

    CAS  PubMed  Google Scholar 

  104. 104

    Carey, A. B. & McLean, R. G. The ecology of rabies: evidence of co-adaptation. J. Appl. Ecol. 20, 777–800 (1983).

    Google Scholar 

  105. 105

    Kuzmin, I. V. et al. Molecular inferences suggest multiple host shifts of rabies viruses from bats to mesocarnivores in Arizona during 2001–2009. PLoS Pathog. 8, e1002786 (2012). This study shows that RABV outbreaks in terrestrial carnivores arose from recurrent reintroductions from bats but found little evidence of adaptive evolution within carnivores.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106

    Lord, R. D. et al. Observations on the epizootiology of vampire bat rabies. Bull. Pan Am. Health Organiz. 9, 189–195 (1975).

    CAS  Google Scholar 

  107. 107

    Slate, D. et al. Oral rabies vaccination in North America: Opportunities, complexities, and challenges. PLoS Negl. Trop. Dis. 3, e549 (2009).

    PubMed  PubMed Central  Google Scholar 

  108. 108

    Streicker, D. G. et al. Host–pathogen evolutionary signatures reveal dynamics and future invasions of vampire bat rabies. Proc. Natl Acad. Sci. USA 113, 10926–10931 (2016).

    CAS  PubMed  Google Scholar 

  109. 109

    Talbi, C. et al. Phylodynamics and human-mediated dispersal of a zoonotic virus. PLoS Pathog. 6, e1001166 (2010).

    PubMed  PubMed Central  Google Scholar 

  110. 110

    Nettles, V. F., Shaddock, J. H., Keith Sikes, R. & Reyes, C. R. Rabies in translocated raccoons. Am. J. Public Health 69, 601–602 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Smith, D. L., Lucey, B., Waller, L. A., Childs, J. E. & Real, L. A. Predicting the spatial dynamics of rabies epidemics on heterogeneous landscapes. Proc. Natl Acad. Sci. USA 99, 3668–3672 (2002).

    CAS  PubMed  Google Scholar 

  112. 112

    Horton, D. L. et al. Complex epidemiology of a zoonotic disease in a culturally diverse region: phylogeography of rabies virus in the Middle East. PLoS Negl. Trop. Dis. 9, e0003569 (2015).

    PubMed  PubMed Central  Google Scholar 

  113. 113

    Zhang, S. et al. Rabies in ferret badgers, Southeastern China. Emerg. Infect. Dis. 15, 946–949 (2009).

    PubMed  PubMed Central  Google Scholar 

  114. 114

    Leslie, M. J. et al. Bat-associated rabies virus in skunks. Emerg. Infect. Dis. 12, 1274 (2006).

    PubMed  PubMed Central  Google Scholar 

  115. 115

    Randall, D. A. et al. Rabies in endangered Ethiopian wolves. Emerg. Infect. Dis. 10, 2214 (2004).

    PubMed  PubMed Central  Google Scholar 

  116. 116

    Streicker, D. G. et al. Host phylogeny constrains cross-species emergence and establishment of rabies virus in bats. Science 329, 676–679 (2010).

    CAS  PubMed  Google Scholar 

  117. 117

    Condori-Condori, R. E., Streicker, D. G., Cabezas-Sanchez, C. & Velasco-Villa, A. Enzootic and epizootic rabies associated with vampire bats, Peru. Emerg. Infect. Dis. 19, 1463–1469 (2013).

    PubMed Central  Google Scholar 

  118. 118

    Duke-sylvester, S. M. et al. Strong seasonality produces spatial asynchrony in the outbreak of infectious diseases. J. R. Soc. Interface 8, 817–825 (2011).

    PubMed  Google Scholar 

  119. 119

    Arechiga-Ceballos, N. et al. New rabies virus variant found during an epizootic in white-nosed coatis from the Yucatan Peninsula. Epidemiol. Infect. 138, 1586–1589 (2010).

    CAS  PubMed  Google Scholar 

  120. 120

    Nadin-Davis, S. et al. A molecular epidemiological study of rabies in Cuba. Epidemiol. Infect. 134, 1313–1324 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. 121

    Nel, L. et al. Mongoose rabies in southern Africa: a re-evaluation based on molecular epidemiology. Virus Res. 109, 165–173 (2005).

    CAS  PubMed  Google Scholar 

  122. 122

    Chiou, H.-Y. et al. Molecular characterization of cryptically circulating rabies virus from ferret badgers, Taiwan. Emerg. Infect. Dis. 20, 790 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Mollentze, N., Biek, R. & Streicker, D. G. The role of viral evolution in rabies host shifts and emergence. Curr. Opin. Virol. 8, 68–72 (2014).

    PubMed  PubMed Central  Google Scholar 

  124. 124

    Hamir, A. N., Moser, G. & Rupprecht, C. E. Clinicopathologic variation in raccoons infected with different street rabies virus isolates. J. Vet. Diagnost. Invest. 8, 31–37 (1996).

    CAS  Google Scholar 

  125. 125

    Sikes, R. K. Pathogenesis of rabies in wildlife. I. Comparative effect of varying doses of rabies virus inoculated into foxes and skunks. Am. J. Vet. Res. 23, 1041–1047 (1962).

    CAS  PubMed  Google Scholar 

  126. 126

    Huang, S., Bininda-Emonds, O. R., Stephens, P. R., Gittleman, J. L. & Altizer, S. Phylogenetically related and ecologically similar carnivores harbour similar parasite assemblages. J. Animal Ecol. 83, 671–680 (2014).

    Google Scholar 

  127. 127

    Longdon, B., Brockhurst, M. A., Russell, C. A., Welch, J. J. & Jiggins, F. M. The evolution and genetics of virus host shifts. PLoS Pathog. 10, e1004395 (2014). This comprehensive review discusses barriers to viral host shifts between species.

    PubMed  PubMed Central  Google Scholar 

  128. 128

    Holmes, E. C., Woelk, C. H., Kassis, R. & Bourhy, H. Genetic constraints and the adaptive evolution of rabies virus in nature. Virology 292, 247–257 (2002).

    CAS  PubMed  Google Scholar 

  129. 129

    Rupprecht, C., Kuzmin, I. & Meslin, F. Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies. F1000Res. 6, 184 (2017).

    PubMed  PubMed Central  Google Scholar 

  130. 130

    Troupin, C. et al. Large-scale phylogenomic analysis reveals the complex evolutionary history of rabies virus in multiple carnivore hosts. PLoS Pathog. 12, e1006041 (2016).

    PubMed  PubMed Central  Google Scholar 

  131. 131

    Streicker, D. G., Altizer, S. M., Velasco-Villa, A. & Rupprecht, C. E. Variable evolutionary routes to host establishment across repeated rabies virus host shifts among bats. Proc. Natl Acad. Sci. USA 109, 19715–19720 (2012).

    CAS  PubMed  Google Scholar 

  132. 132

    Borucki, M. K. et al. Ultra-deep sequencing of intra-host rabies virus populations during cross-species transmission. PLoS Negl. Trop. Dis. 7, e2555 (2013).

    PubMed  PubMed Central  Google Scholar 

  133. 133

    Nel, L. & Rupprecht, C. in Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission (eds Childs, J. E., Mackenzie, J S. & Richt, J. A.) 161–193 (Springer, 2007).

    Google Scholar 

  134. 134

    Eick, G. N., Jacobs, D. S. & Matthee, C. A. A nuclear DNA phylogenetic perspective on the evolution of echolocation and historical biogeography of extant bats (Chiroptera). Mol. Biol. Evol. 22, 1869–1886 (2005).

    CAS  PubMed  Google Scholar 

  135. 135

    Matsumoto, T. et al. Terrestrial animal-derived rabies virus in a juvenile Indian flying fox in Sri Lanka. Jpn. J. Infect. Dis. 70, 693–695 (2017).

    CAS  PubMed  Google Scholar 

  136. 136

    S. H.O.J. I., Y. et al. Genetic characterization of rabies viruses isolated from frugivorous bat (Artibeus spp.) in Brazil. J. Vet. Med. Sci. 66, 1271–1273 (2004).

    CAS  Google Scholar 

  137. 137

    Lee, D. N., Papes, M. & Van Den Bussche, R. A. Present and potential future distribution of common vampire bats in the Americas and the associated risk to cattle. PLoS ONE 7, e42466 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138

    Yuhong, W. Rabies and rabid dogs in sumerian and akkadian literature. J. Am. Oriental Soc. 121, 32–43 (2001).

    Google Scholar 

  139. 139

    Vos, A. et al. The occurrence of rabies in pre-Columbian Central America: an historical search. Epidemiol. Infect. 139, 1445–1452 (2011).

    CAS  PubMed  Google Scholar 

  140. 140

    Velasco-Villa, A. et al. The history of rabies in the Western Hemisphere. Antiviral Res. 146, 221–232 (2017). This review compiles historical information on rabies in the New World, with a focus on the importance of expanding dog populations following European colonization.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. 141

    Scatterday, J. E. Bat rabies in Florida. J. Am. Vet. Med. Assoc. 124, 125 (1954).

    CAS  PubMed  Google Scholar 

  142. 142

    Hayman, D. T., Fooks, A. R., Marston, D. A. & Garcia-R., J. C. The global phylogeography of lyssaviruses — challenging the'out of Africa'hypothesis. PLoS Negl. Trop. Dis. 10, e0005266 (2016).

    PubMed  PubMed Central  Google Scholar 

  143. 143

    Hughes, G. J., Orciari, L. A. & Rupprecht, C. E. Evolutionary timescale of rabies virus adaptation to North American bats inferred from the substitution rate of the nucleoprotein gene. J. Gen. Virol. 86, 1467–1474 (2005).

    CAS  PubMed  Google Scholar 

  144. 144

    Chiba, S. et al. Widespread endogenization of genome sequences of non-retroviral RNA viruses into plant genomes. PLoS Pathog. 7, e1002146 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. 145

    Katzourakis, A. & Gifford, R. J. Endogenous viral elements in animal genomes. PLoS Genet. 6, e1001191 (2010).

    PubMed  PubMed Central  Google Scholar 

  146. 146

    Evans, M. V., Dallas, T. A., Han, B. A., Murdock, C. C. & Drake, J. M. Data-driven identification of potential Zika virus vectors. eLife 6, e22053 (2017).

    PubMed  PubMed Central  Google Scholar 

  147. 147

    Han, B. A., Schmidt, J. P., Bowden, S. E. & Drake, J. M. Rodent reservoirs of future zoonotic diseases. Proc. Natl Acad. Sci. USA 112, 201501598 (2015).

    Google Scholar 

  148. 148

    Nel, L. H. in Sixth Southern and Eastern African Rabies Group Meeting 80–86 (Lilongwe, Malawi, 2001).

    Google Scholar 

  149. 149

    [No authors listed.] Rabies Fact Sheet. World Health Organization http://www.who.int/mediacentre/factsheets/fs099/en/ (2017).

  150. 150

    [No authors listed.] Rabies Vaccine Investment Strategy (GAVI Alliance, 2013).

  151. 151

    Sabeta, C. T. et al. Mokola virus in domestic mammals, South Africa. Emerg. Infect. Dis. 13, 1371–1373 (2007).

    PubMed  PubMed Central  Google Scholar 

  152. 152

    Almeida, M. F., Martorelli, L. F., Aires, C. C., Sallum, P. & Massad, E. Indirect oral immunization of captive vampires, Desmodus rotundus. Virus Res. 111, 77–82 (2005).

    CAS  PubMed  Google Scholar 

  153. 153

    Aguilar-Setién, A. et al. Vaccination of vampire bats using recombinant vaccinia-rabies virus. J. Wildl. Dis. 38, 539–544 (2002).

    PubMed  Google Scholar 

  154. 154

    Aguilar-Sétien, A. et al. Experimental rabies infection and oral vaccination in vampire bats (Desmodus rotundus). Vaccine 16, 1122–1126 (1998). This study demonstrates the first use of recombinant oral rabies vaccines in captive bats.

    Google Scholar 

  155. 155

    Stading, B. et al. Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine. PLoS Negl. Trop. Dis. 11, e0005958 (2017).

    PubMed  PubMed Central  Google Scholar 

  156. 156

    Stading, B. R. et al. Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis). Vaccine 34, 5352–5358 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. 157

    Gomes, M. N., Uieda, W. & Oliveira Latorre, M. d. R. D. d. Influence of sex differences in the same colony for chemical control of vampire Desmodus rotundus (Phyllostomidae) populations in the state of Sao Paulo. Brazil. Pesquisa Veterinária Brasileira 26, 38–43 (2006).

    Google Scholar 

  158. 158

    Johnson, N., Aréchiga-Ceballos, N. & Aguilar-Setien, A. Vampire bat rabies: ecology, epidemiology and control. Viruses 6, 1911–1928 (2014).

    PubMed  PubMed Central  Google Scholar 

  159. 159

    Dürr, S. et al. Rabies diagnosis for developing countries. PLoS Negl. Trop. Dis. 2, e206 (2008).

    PubMed  PubMed Central  Google Scholar 

  160. 160

    Boulger, L. & Porterfield, J. Isolation of a virus from Nigerian fruit bats. Trans. R. Soc. Trop. Med. Hyg. 52, 421–424 (1958).

    CAS  PubMed  Google Scholar 

  161. 161

    Meredith, C., Rossouw, A. & Van Praag, K. An unusual case of human rabies thought to be of chiropteran origin. South Afr. Med. J. 45, 767–769 (1971).

    CAS  Google Scholar 

  162. 162

    Le Gonidec, G., Rickenbach, A., Robin, Y. & Heme, G. Isolement d'une souche de virus Mokola au Cameroun. Annales de Microbiologie 129A, 245–249 (1978).

    Google Scholar 

  163. 163

    Familusi, J., Osunkoya, B., Moore, D., Kemp, G. & Fabiyi, A. A fatal human infection with Mokola virus. Am. J. Trop. Med. Hyg. 21, 959–963 (1972).

    CAS  PubMed  Google Scholar 

  164. 164

    Lembo, T. et al. Exploring reservoir dynamics: a case study of rabies in the Serengeti ecosystem. J. Appl. Ecol. 45, 1246–1257 (2008).

    PubMed  PubMed Central  Google Scholar 

  165. 165

    Gomme, E. A., Wanjalla, C. N., Wirblich, C. & Schnell, M. J. Rabies virus as a research tool and viral vaccine vector. Adv. Virus Res. 79, 139–164 (2011).

    CAS  PubMed  Google Scholar 

  166. 166

    Prehaud, C. et al. Attenuation of rabies virulence: takeover by the cytoplasmic domain of its envelope protein. Sci. Signal. 3, ra5 (2010). This study shows that neuronal survival after infection with RABV was linked to the interaction between a PDZ domain in the carboxy-terminal tail of the RABV glycoprotein and cellular threonine kinases.

    PubMed  Google Scholar 

  167. 167

    Gaudin, Y., Tuffereau, C., Segretain, D., Knossow, M. & Flamand, A. Reversible conformational changes and fusion activity of rabies virus glycoprotein. J. Virol. 65, 4853–4859 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. 168

    Kim, I. S. et al. Mechanism of membrane fusion induced by vesicular stomatitis virus G protein. Proc. Natl Acad. Sci. USA 114, E28–E36 (2017).

    CAS  PubMed  Google Scholar 

  169. 169

    Lloyd-Smith, J. O. et al. Epidemic dynamics at the human-animal interface. Science 326, 1362–1367 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. 170

    Kermack, W. O. & McKendrick, A. G. Contributions to the mathematical theory of epidemics. I. Proc. R. Soc. Med. 115A, 700–721 (1927).

  171. 171

    Freuling, C. M. et al. The elimination of fox rabies from Europe: determinants of success and lessons for the future. Phil. Trans. R. Soc. Lond. B Biol Sci. 368, 20120142 (2013).

    Google Scholar 

  172. 172

    Panjeti, V. G. & Real, L. A. Mathematical models for rabies. Adv. Imag. Electron. Phys. 79, 377–395 (2011).

    Google Scholar 

  173. 173

    Dürr, S. & Ward, M. P. Development of a novel rabies simulation model for application in a non-endemic environment. PLoS Negl. Trop. Dis. 9, e0003876 (2015).

    PubMed  PubMed Central  Google Scholar 

  174. 174

    Johnstone-Robertson, S. P., Fleming, P. J., Ward, M. P. & Davis, S. A. Predicted spatial spread of canine rabies in Australia. PLoS Negl. Trop. Dis. 11, e0005312 (2017).

    PubMed  PubMed Central  Google Scholar 

  175. 175

    Russell, C. A., Smith, D. L., Childs, J. E. & Real, L. A. Predictive spatial dynamics and strategic planning for raccoon rabies emergence in Ohio. PLoS Biol. 3, e88 (2005).

    PubMed  PubMed Central  Google Scholar 

  176. 176

    Lemey, P., Rambaut, A., Drummond, A. J. & Suchard, M. A. Bayesian phylogeography finds its roots. PLoS Comput. Biol. 5, e1000520 (2009).

    PubMed  PubMed Central  Google Scholar 

  177. 177

    Lemey, P., Rambaut, A., Welch, J. J. & Suchard, M. A. Phylogeography takes a relaxed random walk in continuous space and time. Mol. Biol. Evol. 27, 1877–1885 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. 178

    Dellicour, S., Rose, R. & Pybus, O. G. Explaining the geographic spread of emerging viruses: a new framework for comparing viral genetic information and environmental landscape data. BMC Bioinformatics 17, 82 (2016).

    PubMed  PubMed Central  Google Scholar 

  179. 179

    Faria, N. R., Suchard, M. A., Rambaut, A., Streicker, D. G. & Lemey, P. Simultaneously reconstructing viral cross-species transmission history and identifying the underlying constraints. Phil. Trans. R. Soc. Lond. B Biol Sci. 368, 20120196 (2013).

    Google Scholar 

  180. 180

    Brunker, K. et al. Elucidating the phylodynamics of endemic rabies virus in eastern Africa using whole-genome sequencing. Virus Evol. 1, vev011 (2015).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank J. Wilson (Thomas Jefferson University, Philadelphia, PA, USA) for her critical reading and editing of the manuscript. M.J.S. is supported in part by National Institutes of Health grants 1R01AI127823, 1R21AI128175 and 5P40OD010996-12 (P. Strick, University of Pittsburgh, subcontract M.J.S.) and the Jefferson Vaccine Center. D.G.S. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (102507/Z/13/Z).

Author information

Affiliations

Authors

Contributions

C.R.F. and D.G.S. researched data for the article. C.R.F., D.G.S. and M.J.S. made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Matthias J. Schnell.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Reservoirs

Animal species that perpetuate the long-term transmission of a rabies virus strain and can transmit the virus to other species. Sometimes called a reservoir host or maintenance host.

Variants

Viral strains with small genetic differences that may or may not be detectable by antigenic characterization.

RABV-related lyssaviruses

Viruses of the Lyssavirus genus of RNA viruses other than the prototypical member, rabies virus.

Strains

Viral populations maintained within a particular reservoir, often in a geographically defined area that can be genetically distinguished from other sympatric viral populations.

Virions

Infectious particles, complete with the viral genome and viral proteins, capable of transmission to a new cell or host.

Isolates

Viral samples that have been obtained from an infected individual or animal host.

Seroprevalence

The proportion of animals or individuals presenting virus-specific antibodies in their serum, indicative of exposure to either the virus or vaccine.

Spillover infections

Transmission events in which a lyssavirus strain successfully infects an animal of a non-reservoir species.

Phylogroups

Subgeneric classification of lyssavirus species grouped by genetic and immunological characteristics.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fisher, C., Streicker, D. & Schnell, M. The spread and evolution of rabies virus: conquering new frontiers. Nat Rev Microbiol 16, 241–255 (2018). https://doi.org/10.1038/nrmicro.2018.11

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing