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

Isamu Mori, Fumi Goshima, Yoshinori Imai, Shinichi Kohsaka, Tsuyoshi Sugiyama, Tomoaki Yoshida, Takashi Yokochi, Yukihiro Nishiyama, Yoshinobu Kimura

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49 Citations (Scopus)

Abstract

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, Iba 1-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.

Original languageEnglish
Pages (from-to)2109-2116
Number of pages8
JournalJournal of General Virology
Volume83
Issue number9
DOIs
Publication statusPublished - 09-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Virology

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