The Alpha/Beta Interferon Response Controls Tissue Tropism and Pathogenicity of Poliovirus

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Published inJournal of Virology Vol. 79; no. 7; pp. 4460 - 4469
Main Authors IDA-HOSONUMA, Miki, IWASAKI, Takuya, KOIKE, Satoshi, YOSHIKAWA, Tomoki, NAGATA, Noriyo, SATO, Yuko, SATA, Tetsutaro, YONEYAMA, Mitsutoshi, FUJITA, Takashi, TAYA, Choji, YONEKAWA, Hiromichi
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.04.2005
Subjects
Animals
Biological and medical sciences
Central Nervous System - pathology
Central Nervous System - virology
Cercopithecus aethiops
Disease Models, Animal
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Interferon-alpha - physiology
Interferon-beta - immunology
Interferon-beta - physiology
Liver
Mice
Mice, Knockout
Mice, Transgenic
Microbiology
Miscellaneous
Pancreas
Pathogenesis and Immunity
Poliomyelitis - immunology
Poliomyelitis - pathology
Poliomyelitis - virology
Poliovirus
Poliovirus - pathogenicity
Poliovirus - physiology
Receptors, Virus - genetics
Receptors, Virus - physiology
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
RNA, Messenger - analysis
Spleen
Transcription, Genetic
Virology
Virus Replication
Virus
Pathogenicity
Tropism
Microbiology
Picornaviridae
Alpha interferon
Cytokine
Beta interferon
Enterovirus
Poliovirus
Virology
Online AccessGet full text

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Abstract Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JVI .asm.org, visit: JVI       
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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.
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.
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.
Author Hiromichi Yonekawa
Satoshi Koike
Takuya Iwasaki
Noriyo Nagata
Miki Ida-Hosonuma
Choji Taya
Yuko Sato
Tomoki Yoshikawa
Takashi Fujita
Mitsutoshi Yoneyama
Tetsutaro Sata
AuthorAffiliation Department of Microbiology & Immunology, 1 Tokyo Metropolitan Institute for Neuroscience, Department of Tumor Cell Research, 4 Department of Laboratory Animal Sciences, Tokyo Metropolitan Institute of Medical Sciences, Tokyo Metropolitan Organization for Medical Research, 5 Department of Pathology, National Institute of Infectious Diseases, Tokyo, 3 Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan 2
AuthorAffiliation_xml – name: Department of Microbiology & Immunology, 1 Tokyo Metropolitan Institute for Neuroscience, Department of Tumor Cell Research, 4 Department of Laboratory Animal Sciences, Tokyo Metropolitan Institute of Medical Sciences, Tokyo Metropolitan Organization for Medical Research, 5 Department of Pathology, National Institute of Infectious Diseases, Tokyo, 3 Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan 2
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  surname: IDA-HOSONUMA
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  surname: IWASAKI
  fullname: IWASAKI, Takuya
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  surname: KOIKE
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  surname: YOSHIKAWA
  fullname: YOSHIKAWA, Tomoki
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  fullname: NAGATA, Noriyo
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  surname: YONEYAMA
  fullname: YONEYAMA, Mitsutoshi
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  givenname: Takashi
  surname: FUJITA
  fullname: FUJITA, Takashi
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  givenname: Hiromichi
  surname: YONEKAWA
  fullname: YONEKAWA, Hiromichi
  organization: Department of Laboratory Animal Sciences, Tokyo Metropolitan Institute of Medical Sciences, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan
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Issue 7
Keywords Virus
Pathogenicity
Tropism
Microbiology
Picornaviridae
Alpha interferon
Cytokine
Beta interferon
Enterovirus
Poliovirus
Virology
Language English
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Corresponding author. Mailing address: Department of Microbiology & Immunology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Musashidai, Fuchu-shi, Tokyo 183-8526, Japan. Phone: 81-42-325-3881. Fax: 81-42-321-8678. E-mail: koike@tmin.ac.jp.
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Snippet Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley...
Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although poliovirus receptor (PVR) expression is observed in both the target and...
ABSTRACT Poliovirus selectively replicates in neurons in the spinal cord and brainstem, although poliovirus receptor (PVR) expression is observed in both the...
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SubjectTerms Animals
Biological and medical sciences
Central Nervous System - pathology
Central Nervous System - virology
Cercopithecus aethiops
Disease Models, Animal
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Interferon-alpha - physiology
Interferon-beta - immunology
Interferon-beta - physiology
Liver
Mice
Mice, Knockout
Mice, Transgenic
Microbiology
Miscellaneous
Pancreas
Pathogenesis and Immunity
Poliomyelitis - immunology
Poliomyelitis - pathology
Poliomyelitis - virology
Poliovirus
Poliovirus - pathogenicity
Poliovirus - physiology
Receptors, Virus - genetics
Receptors, Virus - physiology
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
RNA, Messenger - analysis
Spleen
Transcription, Genetic
Virology
Virus Replication
Title The Alpha/Beta Interferon Response Controls Tissue Tropism and Pathogenicity of Poliovirus
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