Productive infection in the murine central nervous system with avian influenza virus A (H5N1) after intranasal inoculation

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Abstract
The H5N1 type of influenza A virus isolated from human patients in 1997 has a characteristic hemagglutinin and was considered to be directly transmitted from birds. Although neuropathogenicity of this virus was not demonstrated in human autopsy cases, some experimental studies using mice have disclosed that this virus infects the central nervous system (CNS) after intranasal inoculation. In this study we focused on the topographical localization of virus-infected cells in the murine CNS after intranasal inoculation. We immunohistochemically examined virus-infected cells in mouse tissues using a rabbit antiserum recognizing the nucleoprotein of influenza A virus. The virus-infected cells appeared initially in the respiratory tract. Thereafter, the virus antigen-positive cells appeared in the olfactory system and the cranial nerve nuclei innervating the facial region. This suggests that this virus is principally transmitted from the nasal cavity to CNS through the cranial nerves. Neurons were frequently infected and glial and ependymal cells were also infected. Transneuronal transmission of the virus might play the important role of viral spread within the CNS.