Olfactory receptor neurons prevent dissemination of neurovirulent influenza A virus into the brain by undergoing virus-induced apoptosis

J Gen Virol. 2002 Sep;83(Pt 9):2109-2116. doi: 10.1099/0022-1317-83-9-2109.


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.

MeSH terms

  • Animals
  • Apoptosis*
  • Brain / virology*
  • Calcium-Binding Proteins / analysis
  • Calcium-Binding Proteins / metabolism
  • Central Nervous System Viral Diseases / physiopathology*
  • Central Nervous System Viral Diseases / virology
  • Fas Ligand Protein
  • Female
  • Influenza A virus* / genetics
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins
  • Microglia / metabolism
  • Nerve Degeneration*
  • Olfactory Mucosa / metabolism
  • Olfactory Receptor Neurons / physiopathology*
  • Olfactory Receptor Neurons / virology
  • Proto-Oncogene Proteins c-jun / analysis
  • Proto-Oncogene Proteins c-jun / metabolism
  • Recombination, Genetic
  • Signal Transduction


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Proto-Oncogene Proteins c-jun