Apoptotic neurodegeneration induced by influenza A virus infection in the mouse brain.
Neurodegeneration in the brain induced by the WSN strain of influenza A virus was investigated after stereotaxic introduction into the olfactory bulb of C57BL/6 mice. Immunohistochemistry detected WSN virus-infected neurons in the anterior olfactory nucleus as early as day 3 postinfection. Thereafter, they became shrunken and showed loss of neurite-immunolabeling and chromatin condensation. Infected neurons died by day 12, degenerating into multiple small granular bodies. The terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling method demonstrated DNA fragmentation in infected neurons at day 7 and also in such granular bodies at day 12. In perforin-deficient mice, the appearance of virally induced apoptotic neurodegeneration was delayed and virus infection continued for a longer period of 35 days postinfection. These findings indicate that perforin-mediated neuroapoptosis appears significant in exterminating the intracellular pathogen at an early stage of infection.
Mori
I
I
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Kimura
Y
Y
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D017209:Apoptosis; D001921:Brain / Q000473:pathology* / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000473:pathology* / Q000821:virology; D007150:Immunohistochemistry; D009980:Influenza A virus / Q000276:immunology / Q000302:isolation & purification; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
D000956:Antigens, Viral; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin