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Introduction
Rabies virus (RABV) is the type species of the genus Lyssavirus, within the Rhabdoviridae family. The Rhabdoviridae are negative sense single-stranded RNA viruses with a distinctive bullet-shape structure. A further 10 viruses belong to the Lyssavirus genus and all have caused or have the potential to cause rabies in man. The lyssaviruses have a 12kb genome encoding five proteins [1] , in the order: nucleoprotein (N), phosphoprotein (P), matrix (M), glycoprotein (G) and RNA-dependent-RNA polymerase (L). RABV causes acute encephalitis in mammals with a case fatality rate of almost 100%. The virus persists in endemic cycles within carnivore or chiropteran reservoirs and humans are typically exposed through an animal bite. The majority of human cases occur in Africa and Asia where the dog is the principal vector of transmission. The type of bite varies widely depending on the vector encountered. Dogs can transmit rabies through licking of mucosal surfaces or breaks in the skin. More commonly infection is associated with severe, deep bites, especially in children, and in limbs as victims attempt to defend themselves. Such bites lead to the deposition of virus deep into muscle tissue. By contrast, bats appear to efficiently transmit rabies to humans through shallow, intradermal bites, often going un-noticed by the victim [2] . Aerosol transmission has been observed under extreme conditions [3,4] , however this mechanism is unlikely to contribute to natural transmission of the disease. It is also possible that infection in these cases could have resulted from oral exposure.
Rabies virus, like all members of the Lyssavirus genus, is neurotropic and following a bite infects peripheral nerves close to the bite site. Virus then moves by retrograde axonal transport to the dorsal root ganglia where virus replication becomes detectable [5] . This movement can be extremely rapid. In murine models of infection, amputation or severance of the sciatic nerve following inoculation in the footpad could prevent the development of disease [6] . However, in experimental models this severe method of therapy loses its efficacy within days of inoculation. Axoplasmic transport of rabies virus within cultured rat sensory neurons reached 12-24mm/day [7] . This conflicts with disease in humans where the time period between exposure and the development of rabies can be measured in months, even...