Rabies virus has a broad host range. The virus can infect all mammals, although certain mammals (such as dogs, foxes, wolves, and bats) are important for transmission of infection.
The virus may enter the peripheral nervous system directly at the site of bite. In some cases, however, it may replicate in muscle tissue after entering the host, remaining at or near the site of introduction for most of the incubation period. However, the precise sites of viral sequestration remain unknown, since neither the antigen nor the virus can usually be found in any organ during this phase.
The virus infects the sensory neurons and moves rapidly by axonal transport centripetally to the central nervous system (CNS) for replication. During its transport within the neurons, it is protected from the host immune system. The virus travels along the axons at a rate of 12–24 mm in a day to enter the spinal ganglion.
Its multiplication in the ganglion is indicated by the onset of pain or paresthesia at the site of the inoculum, which are the first clinical symptom and a hallmark finding. From here, the virus spreads quickly, at a rate of 200–400 mm/day, into the CNS, and the spread is marked by rapidly progressive encephalitis. Thereafter, the virus spreads to the periphery and salivary glands (Fig. 64-2).
During the course of infection, encephalitis develops, associ-ated with the death of neurons and demyelination. Acidophilic intracytoplasmic neuronal inclusion bodies are found in infected neurons, which is important for laboratory diagnosis.
Production of cytokines (such as interferon), induced during rabies virus infection or vaccination, has been reported to abort the disease if it occurs shortly after viral infection. Recently, it has been demonstrated that animals immunized with puri-fied RNP complexes or recombinant nucleoprotein vaccines resisted lethal challenge with rabies virus. However, the role of N protein in protection, illness, or recovery is unclear.