Role of Apoptosis in Rabies Viral Encephalitis: A Comparative Study in Mice, Canine, and Human Brain with a Review of Literature

Abstract

To evaluate the role of apoptosis in rabies encephalitis in humans and canines infected with wild-type street virus, in comparison with rodent model infected with street and laboratory passaged CVS strain, we studied postmortem brain tissue from nine humans, six canines infected with street rabies virus, and Swiss albino mice inoculated intramuscularly (IM) and intracerebrally (IC) with street and CVS strains. Encephalitis and high rabies antigen load were prominent in canine and human brains compared to rodents inoculated with street virus. Neuronal apoptosis was detectable only in sucking mice inoculated with CVS strain and minimal in street virus inoculated mice. In a time point study in suckling mice, DNA laddering was noted only terminally (7 days p.i.) following IC inoculation with CVS strain but not with street virus. In weanling and adult mice, apoptosis was restricted to inflammatory cells and absent in neurons similar to human and canine rabies-infected brains. Absence of neuronal apoptosis in wild-type rabies may facilitate intraneuronal survival and replication while apoptosis in inflammatory cells prevents elimination of the virus by abrogation of host inflammatory response.

Perspectives in Diagnosis and Treatment of Rabies Viral Encephalitis: Insights from Pathogenesis

“…On the contrary, using dUTP nick end labeling, we found that many of the inflammatory cells showed apoptotic cell death, which suggests that apoptosis in human rabies is protective rather than pathogenic, and serves as an efficient evasive mechanism of depleting host inflammatory cells, to ensure the survival and propagation of the virus in the infected neurons [113].…”

“…In human rabies, however, studies have conclusively shown that neuronal apoptosis is absent and has no role in natural infection with the wild-type viral strain of rabies [112,113]. On the contrary, using dUTP nick end labeling, we found that many of the inflammatory cells showed apoptotic cell death, which suggests that apoptosis in human rabies is protective rather than pathogenic, and serves as an efficient evasive mechanism of depleting host inflammatory cells, to ensure the survival and propagation of the virus in the infected neurons [113].…”

Apoptosis in natural rabies virus infection in dogs

“…TUNEL positive neurons were seen in all layers of the cerebral cortex, cingulate gyrus, Ammon's horn in the hippocampus, and neurons in the thalamic and hypothalamic regions after infection with CVS strain of rabies virus. In addition to neurons, the inflammatory cells lining the meninges, ependymal cells lining the ventricle, cells of the choroids plexus, and rare glial and microglial cells in the cortex and white matter also showed labelling (21). In spite of the presence of viral antigen, TUNEL reaction does not occur in the Purkinje cells of the cerebellum (12).…”

“…Specific macroscopical lesions are not present, but self-inflicted wounds and foreign bodies in the stomach of a carnivore should raise suspicion. Microscopically, pathognomonic findings are characterised by non-suppurative encephalomyelitis, ganglioneuritis, and parotid adenitis (18,21). For this reason the research projects aim to find the fastest and safest methods of early diagnosis (25,26).…”

Distribución de calbindina y parvoalbúmina y efecto del virus de la rabia sobre su expresión en la médula espinal de ratones

“…En general, la apoptosis no parece ser un fenómeno importante en la fisiopatología de la rabia (30,31). Sin embargo, es posible que el virus genere alteraciones funcionales en las neuronas que expresan esta proteína.…”