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RABIES:

Rabies is an acute encephalitis caused by a virus and is infectious to most mammals.  It is spread from animals to humans. Transmission of rabies is via an infected animal’s saliva usually through a bite though transmission may also occur when an open wound, scratch or mucous membrane is exposed to saliva. The disease manifests itself in two phases, the paralytic and excitable phase.  In non-vaccinated animals, rabies is almost always invariably fatal.  In Western Canada, it is found mostly in carnivores and in several wild species acting as reservoirs for the virus.

The rabies virus: (1)


Classification

Order  Mononegavirales

Family Rhabdoviridae

Genera (3 important genera)

Ephemerovirus

Vesiculovirus

Lyssavirus



www.ivis.org


This last genera includes the rabies virus, Lagos bat, Mokola virus, Duvenhage virus, European bat virus 1 and 2 and the Australian bat virus.
 
Rhabdoviridae are non-segmented and characteristically bullet shaped viruses. (See Figure 1). They are negative-stranded RNA (Ribonucleic acid) viruses which requires an RNA polymerase enzyme to convert it to a positive stranded RNA which can then be transcribed and translated into viral protein (See Figure 3 below)

Figure 1 -  Rabies Virus, note shape



http://www.stanford.edu/group/virus/rhabdo/2004bischoffchang/rabies.gif

                                            
Structure :  (1) 

Viruses of the Rhabdoviridae are 180 nm long and 75 nm wide.
- its genome encodes for five proteins: 
            Nucleoprotein (N)
            Phosphoprotein (P)
            Matrix protein (M)
            Glycoprotein (G)
            Polymerase (L)
 
 Figure 2 - Longitudinal view and cross-section of rabies virus

Image:Rabies virus longitudinal.jpgImage:Rabies virus crosssection.jpg

http://upload.wikimedia.org/wikipedia/commons/2/26/Rabies_virus_crosssection.jpg
http://upload.wikimedia.org/wikipedia/commons/b/b4/Rabies_virus_longitudinal.jpg

Pathogenesis:  (4)

Rabies is a viral zoonosis and therefore can be passed between humans and animals, which is another reason why vaccination protocols are crucial (See Vaccination Protocols and Legislature). Most infections result from a bite or scratch of an infected animal. Transmission is through the animal's saliva which is contaminated with the rabies virus, and when it comes into contact with the victim's mucous membrane, skin lesions, etc... the virus is spread.
 
The rabies virus has a selective affinity for nervous tissue but it first binds itself to receptors present on the muscle cells of the bite wound. The time of infection to the onset of clinical signs varies with i) the amount of virus acquired through the bite, ii) how much the tissue is innervated and iii) its proximity to the brain.  The larger the dose received and the closer the to the central nervous system, the faster the onset of signs. It can vary from 4 days to several years, though on average it is between 20 and 90 days.  This is another reason why quarantine and adherence to vaccination protocols are important for future travels.  (See VACCINES AND PROTOCOLS)

 Figure 3 - Viral incorporation and replication


http://0-www.cdc.gov.mill1.sjlibrary.org/ncidod/dvrd/rabies/the_virus/images/cycbig.jpg

Steps in Virus Infection and Replication:
(See Figure 3 above)

Adsorption: This is the initial step where the virus through the interaction of cell receptors and viral proteins, the virus adheres to the host cell's surface.

Penetration:  Viral entry into the host cell.

Uncoating:  Removal of viral envelope exposing its genetic material (NB:  Rhabdoviridae are negative stranded RNA viruses)

Transcription:  Rhabdoviridae are negative stranded RNA viruses which requires a RNA polymerase enzyme to convert it to a positive stranded segment of mRNA prior to translation.

mRNA: RNA that serves as a template for protein synthesis.  xray.bmc.uu.se/~kenth/bioinfo/glossary.html

Translation: the process by which the mRNA code is converted to a sequence of amino acids (a protein). genome.pfizer.com/glossary.cfm

Replication:  amplification of the virus genetic material in the host cell.

Assembly:  assembly of viral components

Budding:  complete viruses emerge from host cell.

(reference: 10 and 18)