Apoptosis in experimental rabies in bax-deficient mice.
The challenge virus standard (CVS) of fixed rabies virus produces a fatal encephalitis in adult and suckling mice after intracerebral inoculation. The infection is associated with apoptotic cell death in brain neurons and increased immunoreactivity to the Bax protein in the hippocampus and cerebral cortex. Five- to 7-day-old bax-deficient mice and their wild-type littermates were inoculated intracerebrally with either CVS or the RV194-2 variant of rabies virus, which is avirulent in adult mice after intracerebral inoculation. The clinical disease was similar with both viruses in bax-deficient and wild-type mice with 100% mortality. CVS produced similar apoptotic changes in bax-deficient and wild-type mice, except that apoptosis was more marked in neurons of the dentate gyrus and cortical neurons in the wild-type mice. After inoculation with RV194-2, the morphologic changes of apoptosis were markedly less severe in the cerebral cortex, hippocampus, and cerebellum of the bax-deficient mice than wild-type mice. However, apoptotic changes were moderate to severe in the brain stem in both wild-type and bax-deficient mice with both viruses. Although apoptotic cell death was much less prominent in bax-deficient mice after inoculation with RV194-2, apoptosis of infected brain stem neurons occurred in this fatal infection. Although the Bax protein plays an important role in modulating rabies virus-induced apoptosis under specific experimental conditions, other modulators are also likely important.
Jackson
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AC
Department of Medicine, Queen's University, Kingston, Ontario, Canada. jacksona@post.queensu.ca
D000818:Animals; D017209:Apoptosis; D001933:Brain Stem / Q000473:pathology / Q000821:virology; D002540:Cerebral Cortex / Q000473:pathology / Q000821:virology; D018891:Dentate Gyrus / Q000473:pathology / Q000821:virology; D018792:Encephalitis, Viral / Q000473:pathology* / Q000821:virology; D005838:Genotype; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D017966:Pyramidal Cells / Q000473:pathology / Q000821:virology; D011818:Rabies / Q000473:pathology*; D011820:Rabies virus / Q000472:pathogenicity*; D014774:Virulence; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein