Olfactory receptor neurons prevent dissemination of neurovirulent influenza A virus into the brain by undergoing virus-induced apoptosis.
Olfactory receptor neurons (ORNs) were infected upon intranasal inoculation with the R404BP strain of neurovirulent influenza A virus. Virus-infected neurons and a small fraction of neighbouring uninfected neurons displayed apoptotic neurodegeneration substantiated by the immunohistochemistry for activated caspase-3 molecules and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling method. However, virus infection was restricted within the peripheral neuroepithelium and all mice survived the infection. Virus-infected ORNs revealed upregulated expression of the Fas ligand molecules, activating the c-Jun N-terminal kinase signal transduction pathway. In addition, Iba1-expressing activated microglia/macrophages appeared to partake in phagocytic activities, eventually clearing apoptotic bodies. These results raise the possibility that induction of apoptosis in olfactory receptor neurons at an early stage of infection may provide protective effects against invasion of the neurovirulent virus from the peripheral to the CNS.
Mori
Isamu
I
Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan3.|Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi, Japan2.|Department of Microbiology, Fukui Medical University School of Medicine, 23-3 Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan1.
Goshima
Fumi
F
Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan3.
Imai
Yoshinori
Y
Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan4.
Kohsaka
Shinichi
S
Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan4.
Sugiyama
Tsuyoshi
T
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi, Japan2.
Yoshida
Tomoaki
T
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi, Japan2.
Yokochi
Takashi
T
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Aichi, Japan2.
Nishiyama
Yukihiro
Y
Laboratory of Virology, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Aichi, Japan3.
Kimura
Yoshinobu
Y
Department of Microbiology, Fukui Medical University School of Medicine, 23-3 Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan1.
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000821:virology*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism; D020805:Central Nervous System Viral Diseases / Q000503:physiopathology* / Q000821:virology; D053222:Fas Ligand Protein; D005260:Female; D009980:Influenza A virus / Q000235:genetics; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration; D009831:Olfactory Mucosa / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000503:physiopathology* / Q000821:virology; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D016755:Proto-Oncogene Proteins c-jun