This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ida-Hosonuma, M. Articles by Koike, S. Search for Related Content PubMed PubMed Citation Articles by Ida-Hosonuma, M. Articles by Koike, S.

 Previous Article  |  Next Article 

Journal of Virology, April 2005, p. 4460-4469, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4460-4469.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

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, Japan²

Received 29 August 2004/ Accepted 12 November 2004

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.

This article has been cited by other articles:

• Khan, S., Peng, X., Yin, J., Zhang, P., Wimmer, E. (2008). Characterization of the New World Monkey Homologues of Human Poliovirus Receptor CD155. J. Virol. 82: 7167-7179 [Abstract] [Full Text]  
• Arita, M., Ami, Y., Wakita, T., Shimizu, H. (2008). Cooperative Effect of the Attenuation Determinants Derived from Poliovirus Sabin 1 Strain Is Essential for Attenuation of Enterovirus 71 in the NOD/SCID Mouse Infection Model. J. Virol. 82: 1787-1797 [Abstract] [Full Text]  
• Ireland, D. D. C., Stohlman, S. A., Hinton, D. R., Atkinson, R., Bergmann, C. C. (2008). Type I Interferons Are Essential in Controlling Neurotropic Coronavirus Infection Irrespective of Functional CD8 T Cells. J. Virol. 82: 300-310 [Abstract] [Full Text]  
• Ohka, S., Igarashi, H., Nagata, N., Sakai, M., Koike, S., Nochi, T., Kiyono, H., Nomoto, A. (2007). Establishment of a Poliovirus Oral Infection System in Human Poliovirus Receptor-Expressing Transgenic Mice That Are Deficient in Alpha/Beta Interferon Receptor. J. Virol. 81: 7902-7912 [Abstract] [Full Text]  
• Zhou, Z., Hamming, O. J., Ank, N., Paludan, S. R., Nielsen, A. L., Hartmann, R. (2007). Type III Interferon (IFN) Induces a Type I IFN-Like Response in a Restricted Subset of Cells through Signaling Pathways Involving both the Jak-STAT Pathway and the Mitogen-Activated Protein Kinases. J. Virol. 81: 7749-7758 [Abstract] [Full Text]  
• Han, J.-Q., Townsend, H. L., Jha, B. K., Paranjape, J. M., Silverman, R. H., Barton, D. J. (2007). A Phylogenetically Conserved RNA Structure in the Poliovirus Open Reading Frame Inhibits the Antiviral Endoribonuclease RNase L. J. Virol. 81: 5561-5572 [Abstract] [Full Text]  
• Smura, T. P., Junttila, N., Blomqvist, S., Norder, H., Kaijalainen, S., Paananen, A., Magnius, L. O., Hovi, T., Roivainen, M. (2007). Enterovirus 94, a proposed new serotype in human enterovirus species D. J. Gen. Virol. 88: 849-858 [Abstract] [Full Text]  
• Nakatsu, Y., Takeda, M., Ohno, S., Koga, R., Yanagi, Y. (2006). Translational Inhibition and Increased Interferon Induction in Cells Infected with C Protein-Deficient Measles Virus. J. Virol. 80: 11861-11867 [Abstract] [Full Text]  
• Yanagi, Y., Takeda, M., Ohno, S. (2006). Measles virus: cellular receptors, tropism and pathogenesis.. J. Gen. Virol. 87: 2767-2779 [Abstract] [Full Text]  
• Merrill, M. K., Gromeier, M. (2006). The Double-Stranded RNA Binding Protein 76:NF45 Heterodimer Inhibits Translation Initiation at the Rhinovirus Type 2 Internal Ribosome Entry Site. J. Virol. 80: 6936-6942 [Abstract] [Full Text]  
• Yoshikawa, T., Iwasaki, T., Ida-Hosonuma, M., Yoneyama, M., Fujita, T., Horie, H., Miyazawa, M., Abe, S., Simizu, B., Koike, S. (2006). Role of the Alpha/Beta Interferon Response in the Acquisition of Susceptibility to Poliovirus by Kidney Cells in Culture. J. Virol. 80: 4313-4325 [Abstract] [Full Text]  
• Lopez, C. B., Yount, J. S., Hermesh, T., Moran, T. M. (2006). Sendai Virus Infection Induces Efficient Adaptive Immunity Independently of Type I Interferons. J. Virol. 80: 4538-4545 [Abstract] [Full Text]  
• Pfeiffer, J. K., Kirkegaard, K. (2006). Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain. Proc. Natl. Acad. Sci. USA 103: 5520-5525 [Abstract] [Full Text]  
• Kauder, S., Kan, S., Racaniello, V. R. (2006). Age-Dependent Poliovirus Replication in the Mouse Central Nervous System Is Determined by Internal Ribosome Entry Site-Mediated Translation. J. Virol. 80: 2589-2595 [Abstract] [Full Text]  
• Yoneyama, M., Kikuchi, M., Matsumoto, K., Imaizumi, T., Miyagishi, M., Taira, K., Foy, E., Loo, Y.-M., Gale, M. Jr, Akira, S., Yonehara, S., Kato, A., Fujita, T. (2005). Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity. J. Immunol. 175: 2851-2858 [Abstract] [Full Text]