This review has highlighted the Rabies virus entry to the body and its transport to the central nervous system (CNS) and effect on neurons. Rabies virus causes a rapidly fatal neurological disease with an incubation period, lasting 20 to 90 days or even longer than 1 year. The centripetal spread of this virus within the CNS occurs by fast axonal transport at a rate of 12 to 100 mm per day. This transport exclusively occurs in the retrograde direction. From the inoculation site, it enters into the nervous system from the muscular system through neuromuscular junction, by binding to nicotinic acetylcholine receptors. It also binds to neural cell adhesion molecules and the P75 neurotrophic receptor. It has been seen that rabies virus phosphoprotein strongly interacts with the 10- kDa cytoplasmic dyenin light chain (LC8). However, LC8 has been showed to be dispensable in young mice for the spread of pathogenic rabies virus from the PNS to CNS. At later stage, it has been reported that glycoprotein plays important role in transsynaptic spread of rabies virus between neurons.
Neuronal dysfunction, rather than neuronal cell death, is considered as responsible clinical feature. Naturally, rabies is characterized by severe neurologic signs and fatal outcome with relatively mild neuropathologic changes in the CNS, supporting the idea of occurrence of neuronal dysfunction, rather than neuronal cell death, which plays the pivotal role in producing the disease. Ion channel dysfunction has been seen in the cultured neuroblastoma NA cells of rabies virus infected mouse. The infection is found to reduce the functional expression of voltage dependant sodium channels and inward rectifier potassium channels, and decreased resting membrane potential, which reflects membrane depolarization. Moreover, induction of inducible nitric oxide synthase (iNOS) mRNA and increased brain levels of nitric oxide has been demonstrated in the infected rodents. However, the significance of this finding needs further clarification.
Neurotropic viruses such as rabies virus cause cell death by either apoptosis or necrosis. The challenge virus strain (CVS) of fixed rabies virus has been seen to induce apoptotic cell death in the mouse neuroblastoma cells and mouse embryonic hippocampal neurons. Prominent apoptosis has been observed in the mice brain of various ages inoculated intracerebrally with the CVS strain of fixed rabies virus. However, different neuronal cell types respond differently to the infection, and the presence of glial cells and/or neurons other than motor neurons are essential for apoptosis of spinal motor neurons. Synaptic contact with spinal cord neurons or physical contact with glial cell may be necessary for induction of apoptotic cell death in the motor neurons, but not for apoptosis of the neurons in the hippocampus. In the rabies virus infection, there are complex cellular mechanisms involved in the cell death process or the neuronal survival both in vitro or in vivo using different viral strains and routes of inoculation.
Reference:
Alan C. Jackson (2003). Rabies virus infection: An update. , 9(2), 253–258. doi:10.1080/13550280390193975
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