title: Comparison of neuropathogenicity of poliovirus in two transgenic mouse strains expressing human poliovirus receptor with different distribution patterns.
abstract: In order to determine the influence of poliovirus receptor (PVR) expression on poliovirus cell tropism and neuropathogenesis, two transgenic (tg) mouse models were produced in which PVR was expressed under the transcriptional control of the human PVR gene promoter (hg-PVR mice) and the CAG promoter (CAG-PVR mice). Then the pathogenicity of poliovirus after intracerebral inoculation of the type 1 Mahoney strain was compared. These showed completely different clinical and pathological changes. In the former, the expression of PVR in neurons in the central nervous system (CNS) conferred susceptibility to poliovirus, and a paralytic disease that resembled the human poliomyelitis occurred. In the latter, PVR expression was detected in glial and ependymal cells in addition to the neurons. Paralysis of the limbs and death were rarely observed and mice survived without showing substantial clinical abnormality. Histopathological examination revealed that glial and ependymal cells also became susceptible to poliovirus infection. Poliovirus antigens were mainly detected in ependymal and glial cells and hippocampal neurons near the lateral ventricles in the brain, but were not frequently detected in neurons in the brainstem unlike in the hg-PVR mice. The levels of viral antigens and virus recovered from the CNS of CAG-PVR mice began to decrease as early as 2 days after inoculation, which suggested induction of a fast immune response. These results suggest that the neuropathogenicity of poliovirus changes markedly depending on the specific expression of the PVR molecule in the CNS.
authors.affiliation: Department of Microbiology and Immunology, The Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo 183-8526, Japan1.
authors.forename: Miki
authors.initials: M
authors.lastname: Ida-Hosonuma
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama-cho, Shinjuku-ku, Tokyo 162-8540, Japan2.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan3.
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama-cho, Shinjuku-ku, Tokyo 162-8540, Japan2.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Microbiology and Immunology, The Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo 183-8526, Japan1.
authors.forename: Jifen
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama-cho, Shinjuku-ku, Tokyo 162-8540, Japan2.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan3.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.affiliation: Department of Microbiology and Immunology, The Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-shi, Tokyo 183-8526, Japan1.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koike
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000473:pathology* / Q000821:virology; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011051:Poliomyelitis / Q000401:mortality / Q000473:pathology* / Q000821:virology; D017955:Poliovirus / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; C066100:poliovirus receptor