Rabies: Virus and Disease

Susan A Nadin‐Davis, Centre of Expertise for Rabies, Ottawa, Ontario, Canada

Published online: December 2010

DOI: 10.1002/9780470015902.a0002244.pub2

Rabies is an acute encephalomyelitis, caused by a group of genetically related lyssaviruses. The primary sources of rabies are major animal reservoirs in the orders Chiroptera and Carnivora, although this deadly zoonosis may affect all mammals, including humans. Despite the availability of biologicals that are efficacious in preventing the disease, once clinical signs develop, the disease is almost invariably fatal and kills over 50 000 people annually. The most effective control measures involve parenteral dog vaccination and oral vaccination of wildlife. Genetic analysis of lyssaviruses is extending our understanding of their diversity and evolution. The mechanisms that contribute to viral pathogenesis are being explored by studying the molecular interactions of the viral components with host cell factors. Such knowledge may provide for new less costly vaccines and effective therapeutic interventions in the future.

Key Concepts:

  • Rabies is a neurological disease that can affect almost all mammals and is almost invariably fatal once clinical signs develop.
  • Rabies is caused by all members of the Lyssavirus genus, bullet-shaped neurotropic viruses with small RNA genomes, which are normally transmitted in virus-laden saliva through bites.
  • Humans rarely transmit the disease to other humans but are exposed through contact with rabid animals.
  • Prevention of human disease is undertaken by a regimen of timely post-exposure prophylaxis.
  • Distinct Lyssavirus species and variants thereof are maintained in dogs in the developing world and by several wildlife species including foxes, skunks, raccoons, raccoon dogs, mongooses, jackals and many species of bats.
  • Through a series of viral–host interactions, rabies virus has evolved mechanisms that maintain the neural network required for its propagation and spread within the infected host while avoiding clearance by the host's immune system.
  • Knowledge of the diversity of the Lyssavirus genus is steadily expanding with increased surveillance and development of molecular tools to enable rapid characterisation of new isolates.
  • Current vaccines and biologicals are ineffective against the more diverse members of the genus thereby indicating that additional novel reagents may be required in the future.
  • Ultimately, control and eradication of rabies will require elimination of the disease from animal reservoirs through the application of efficacious and cost-effective methods of animal vaccination.

Keywords: rabies; hydrophobia; Rhabdovirus; Lyssavirus; mad dog; encephalitis; zoonoses; animal reservoirs; prophylaxis

Figure 1. Rabies virions are bullet-shaped and measure approximately 180 nm in length and 75 nm in diameter. The outer surface is covered by 10-nm spike-like glycoprotein peplomers. The basic structure and composition is depicted in the longitudinal diagram. The internal construction of the virion is portrayed in the cross-sectional diagram.
Figure 2. The cycle of replication and infection in lyssaviruses involves: (1) adsorption; (2) penetration; (3) uncoating; (4) transcription; (5) translation; (6) processing; (7) replication; (8) assembly and (9) budding.
Figure 3. A schematic showing the organisation of the rabies virus genome (Pasteur Virus (PV) strain (Genbank accession number M)), which is a single-stranded, antisense, nonsegmented RNA of approximately 12 kb. A leader (Le) sequence of 58 nucleotides at the 3¢ terminus is followed by N, P, M, G and L genes, which code for the five structural proteins and a 70 nucleotide trailer (Tr) sequence at the 5¢ terminus. The intergenic nontranslated regions (NC) are considered variable, especially between G and L genes. The numbers below each gene are the length, in nucleotides, of the mRNA transcripts for each gene. Amino acid lengths of the proteins are N (450), P (297), M (202), G (524, 505 after processing) and L (2142). Minor length variations are observed in some other lyssaviruses. The arrow at bottom indicates the direction of transcription with the transcription gradient represented in colour from black (high) to grey (low).
Figure 4. A phylogenetic analysis of 80 viral isolates representative of known Lyssavirus diversity. The phylogenetic tree was generated from an alignment of complete N gene coding sequences (1350 bases) produced using the CLUSTALX package (available from http://www.clustal.org/) and analysed by the neighbour joining method implemented in MEGA version 4 software (available from http://www.megasoftware.net/). The N gene sequence of the vesicular stomatitis virus (Indiana subtype) was used as an outgroup (branch not shown). Subdivision of the genus into its two phylogroups is shown in colour (grey for 1 and red for 2). Species assignments of all clades are shown to the far right of the figure with inclusion of the tentative new species SHIBV. The subdivision of the rabies virus species into seven established viral clades is also indicated by the colour-coded boxes thus: Cosmopolitan, Arctic/Arctic-like. Africa 2,3, India, Asia and American indigenous. To the left of each clade name, the countries affected and the main reservoir species are indicated. The scale in the upper left corner depicts the genetic distances represented by all horizontal lines in the tree. Bootstrap values >70%, which strongly support the illustrated branch patterns, are shown in blue either below or to the left of many major branch points. The country of origin of each isolate employed in this analysis is indicated by a two- or three-letter suffix, thus, AFS, Republic of South Africa; ALL, Germany; ARS, Republic of Saudi Arabia; AUS, Australia; BIR, Myanmar; BRZ, Brazil; CAM, Cameroon; CAN, Canada; CBG, Cambodia; CH, Chile; CHI, China; COL, Columbia; EST, Estonia; ETH, Ethiopia; FIN, Finland; FRA, France; GUI, Guinea; GUY, French Guyana; HAV, Burkina Faso; IN, India; IND, Indonesia; IRN, Iran; ISL, Israel; KYA, Kenya; KYR, Kyrgizstan; MAR, Morocco; MEX, Mexico; MOZ, Mozambique; NAM, Namibia; NEP, Nepal; NIG, Nigeria; NTH, The Netherlands; PAK, Pakistan; POL, Poland; PR, Peru; RUS, Russia; SRL, Sri Lanka; TAJ, Tajikistan; TAN, Tanzania; TD, Trinidad; THA, Thailand; US, United States of America (preceded by state); YAK, Yakutia (Siberia); YOU, former Republic of Yugoslavia and ZIM, Zimbabwe.
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Related Sub-Topics:

Virus Diseases | Viruses Infecting Humans | RNA Viruses | Viruses Infecting Animals
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Article Title: Rabies: Virus and Disease
 
How to Cite close
Nadin‐Davis, Susan A(Dec 2010) Rabies: Virus and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002244.pub2]