Pathogenesis of rabies.
Rabies is a central nervous system (CNS) disease that is almost invariably fatal. The causative agent is rabies virus (RV), a negative-stranded RNA virus of the rhabdovirus family. RV pathogenesis, like that of other viruses, is a multigenic trait. Recent findings indicate that in addition to the RV G protein viral elements that regulate gene expression, especially expression of the L gene, are also likely to play a role in RV pathogenesis. In vivo, RV infects almost exclusively neurons, and neuroinvasiveness is the major defining characteristic of a classical RV infection. A key factor in the neuroinvasion of RV is transsynaptic neuronal spread. While the ability of RV to spread from the post-synaptic site to the pre-synaptic site is mediated by the RV G protein, the RV P protein might be an important determinant of retrograde transport of the virus within axons. Although the mechanism(s) by which an RV infection cause(s) a lethal neurological disease are still not well understood, the most significant factor underlying the lethal outcome of an RV infection appears to be the neuronal dysfunction due to drastically inhibited synthesis of proteins required in maintaining neuronal functions.
Department of Microbiology, Center for Neurovirology, Thomas Jefferson University, Philadelphia, PA, USA. Bernhard.dietzschold@jefferson.edu
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Dietzschold
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Schnell
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Koprowski
D000818:Animals; D000956:Antigens, Viral / Q000502:physiology; D020805:Central Nervous System Viral Diseases / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D012321:DNA-Directed RNA Polymerases / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D018832:Molecular Chaperones; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010750:Phosphoproteins / Q000502:physiology; D011818:Rabies / Q000473:pathology* / Q000503:physiopathology / Q000821:virology*; D011820:Rabies virus / Q000472:pathogenicity* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology; D015678:Viral Structural Proteins / Q000502:physiology; D014779:Virus Replication
D000956:Antigens, Viral; D006023:Glycoproteins; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; C064951:glycoprotein G, Rabies virus; C097625:L protein, Rabies virus; D012321:DNA-Directed RNA Polymerases