title: The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus.
abstract: Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although poliovirus receptor (PVR) expression is observed in both the target and nontarget tissues in humans and transgenic mice expressing human PVR (PVR-transgenic mice). We assessed the role of alpha/beta interferon (IFN) in determining tissue tropism by comparing the pathogenesis of the virulent Mahoney strain in PVR-transgenic mice and PVR-transgenic mice deficient in the alpha/beta IFN receptor gene (PVR-transgenic/Ifnar knockout mice). PVR-transgenic/Ifnar knockout mice showed increased susceptibility to poliovirus. After intravenous inoculation, severe lesions positive for the poliovirus antigen were detected in the liver, spleen, and pancreas in addition to the central nervous system. These results suggest that the alpha/beta IFN system plays an important role in determining tissue tropism by protecting nontarget tissues that are potentially susceptible to infection. We subsequently examined the expression of IFN and IFN-stimulated genes (ISGs) in the PVR-transgenic mice. In the nontarget tissues, ISGs were expressed even in the noninfected state, and the expression level increased soon after poliovirus infection. On the contrary, in the target tissues, ISG expression was low in the noninfected state and sufficient response after poliovirus infection was not observed. The results suggest that the unequal IFN response is one of the important determinants for the differential susceptibility of tissues to poliovirus. We consider that poliovirus replication was observed in the nontarget tissues of PVR-transgenic/Ifnar knockout mice because the IFN response was null in all tissues.
authors.affiliation: Department of Microbiology & Immunology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo 183-8526, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Ida-Hosonuma
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yoneyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koike
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000473:pathology / Q000821:virology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000276:immunology* / Q000502:physiology*; D008099:Liver; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010179:Pancreas; D011051:Poliomyelitis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D017955:Poliovirus / Q000472:pathogenicity* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology; D013154:Spleen; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D012333:RNA, Messenger; D011991:Receptors, Virus; D016899:Interferon-beta