title: Diabolical effects of rabies encephalitis.
abstract: Rabies is an acute encephalomyelitis in humans and animals caused by rabies virus (RABV) infection. Because the neuropathological changes are very mild in rabies, it has been assumed that neuronal dysfunction likely explains the severe clinical disease. Recently, degenerative changes have been observed in neuronal processes (dendrites and axons) in experimental rabies. In vitro studies have shown evidence of oxidative stress that is caused by mitochondrial dysfunction. Recent work has shown that the RABV phosphoprotein (P) interacts with mitochondrial Complex I leading to overproduction of reactive oxygen species, which results in injury to axons. Amino acids at positions 139 to 172 of the P are critical in this process. Rabies vectors frequently show behavioral changes. Aggressive behavior with biting is important for transmission of the virus to new hosts at a time when virus is secreted in the saliva. Aggression is associated with low serotonergic activity in the brain. Charlton and coworkers performed studies in experimentally infected striped skunks with skunk rabies virus and observed aggressive behavioral responses. Heavy accumulation of RABV antigen was found in the midbrain raphe nuclei, indicating that impaired serotonin neurotransmission from the brainstem may account for the aggressive behavior. We now have an improved understanding of how RABV causes neuronal injury and how the infection results in behavioral changes that promote viral transmission to new hosts.
authors.affiliation: Department of Internal Medicine (Neurology), University of Manitoba, Winnipeg, Manitoba, Canada. ajackson2@hsc.mb.ca.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada. ajackson2@hsc.mb.ca.|Health Sciences Centre, GF-543, 820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada. ajackson2@hsc.mb.ca.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Jackson
mesh_terms: D000374:Aggression; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D018792:Encephalitis, Viral / Q000378:metabolism / Q000503:physiopathology / Q000635:transmission / Q000821:virology*; D054884:Host-Pathogen Interactions; D012889:Mephitidae / Q000821:virology; D066267:Midbrain Raphe Nuclei / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018832:Molecular Chaperones; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011818:Rabies / Q000378:metabolism / Q000503:physiopathology / Q000635:transmission / Q000821:virology*; D011820:Rabies virus / Q000235:genetics / Q000472:pathogenicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D018832:Molecular Chaperones; C103961:P phosphoprotein, Rabies virus; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D015678:Viral Structural Proteins; D012701:Serotonin; D042967:Electron Transport Complex I
keywords: Aggressive behavior; Mitochondrial dysfunction; Oxidative stress; Pathogenesis; Rabies; Serotonin; Viral encephalitis