|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
I. In mice inoculated by various routes, the routes of infection, in descending order if efficacy, were intracerebral, intranasal, subcutaneous, intraperitoneal, intravenous and oral. In mice inoculated by subcutaneous route in hind leg, viral antigen was detected immunohistochemically in neurons of the lumbar spinal cord, cerebral cortex, and in Purkinje cells of cerebellum.
II. The virus spread was detected in the regenerating axons but not in the Schwann cells of peripheral nerves of rats, suggesting that the virus might spread from peripheral nerves to the CNS trans-synaptically as same as rabies virus.
III. The infected cells were identified immunohistochemically as neurons by double or triple staining using anti-HEV antibody with anti-GFAP (astrocytes) antibody or TB-4 (microglial) antibody.
IV. From these results, 1) the virus spreads in axons trans-synaptically from peripheral nerve to the CNS, 2) the Virus-targeting cells are neurons, 3) the infected neurons appeared to be non-cytopathological. 4) the cellular responses were not detected in the CNS.
These neurotropic properties of HEV are responsible for persistent infection, virus-travelling from peripheral nerves to the CNS by trans-synaptic pathways.