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The Vagus Nerve is One Route of Transneural Invasion for Intranasally Inoculated Influenza A Virus in Mice

Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan (KM, CHP, YS, TK, KO, TU); and Laboratory of Microbiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan (HK)

Intranasally inoculated neurotropic influenza viruses in mice infect not only the respiratory tract but also the central nervous system (CNS), mainly the brain stem.^26,34 Previous studies suggested that the route of invasion of virus into the CNS was via the peripheral nervous system, especially the vagus nerve. To evaluate the transvagal transmission of the virus, we intranasally inoculated unilaterally vagectomized mice with a virulent influenza virus (strain 24a5b) and examined the distribution of the viral protein and genome by immunohistochemistry and in situ hybridization over time. An asymmetric distribution of viral antigens was observed between vagal (nodose) ganglia: viral antigen was detected in the vagal ganglion of the vagectomized side 2 days later than in the vagal ganglion of the intact side. The virus was apparently transported from the respiratory mucosa to the CNS directly and decussately via the vagus nerve and centrifugally to the vagal ganglion of the vagectomized side. The results of this study, thus, demonstrate that neurotropic influenza virus travels to the CNS mainly via the vagus nerve.

Key words: Immunohistochemistry; influenza A virus; in situ hybridization; mice; peripheral nerve; vagal ganglion; vagus nerve.

Request reprints from Dr. T. Umemura, Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818 (Japan). E-mail: umemura{at}vetmed.hokudai.ac.jp.

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