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Journal of Virology, March 2006, p. 2589-2595, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2589-2595.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Age-Dependent Poliovirus Replication in the Mouse Central Nervous System Is Determined by Internal Ribosome Entry Site-Mediated Translation

Steven Kauder,{dagger} Sherry Kan,{ddagger} and Vincent R. Racaniello*

Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032

Received 2 June 2005/ Accepted 21 December 2005

Mouse cells are not permissive for the replication of human rhinovirus type 2 (HRV2). To determine the role of the HRV2 internal ribosome entry site (IRES) in determining species specificity, a recombinant poliovirus (P1/HRV2) was constructed by substituting the poliovirus IRES with the IRES from HRV2. This recombinant virus replicated in all human and murine cell lines examined, demonstrating that the HRV2 IRES does not limit viral replication in transformed murine cells. P1/HRV2 replicated in the brain and spinal cord in neonatal but not adult mice transgenic for the poliovirus receptor, CD155. Passage of P1/HRV2 in mice led to selection of a virus that caused paralysis in neonatal mice. To determine the relationship between HRV2 IRES-mediated translation and replication of P1/HRV2 in mice, recombinant human adenoviruses were used to express bicistronic mRNAs in murine organs. The results demonstrate that the HRV2 IRES mediates translation in organs of neonatal but not adult mice. These findings show that HRV2 IRES-mediated translation is a determinant of virus replication in the murine brain and spinal cord and suggest that the IRES determines the species specificity of HRV2 infection.


* Corresponding author. Mailing address: Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-5707. Fax: (212) 305-5106. E-mail: vrr1{at}columbia.edu.

{dagger} Present address: Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141-9100.

{ddagger} Present address: The Rockefeller University, New York, NY 10021.


Journal of Virology, March 2006, p. 2589-2595, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2589-2595.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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