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Journal of Virology, February 1999, p. 958-964, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Dual Stem Loops within the Poliovirus Internal Ribosomal Entry Site Control Neurovirulence

Matthias Gromeier,1,* Birgit Bossert,1 Mineo Arita,2 Akio Nomoto,2 and Eckard Wimmer1

Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794,1 and Department of Microbiology, Institute of Medical Science, University of Tokyo, Tokyo, Japan2

Received 20 July 1998/Accepted 2 November 1998

In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5' nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity.

* Corresponding author. Mailing address: Dept. of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794. Phone: (516) 632-8806. Fax: (516) 632-8891. E-mail: gromeier{at}asterix.bio.sunysb.edu.

Journal of Virology, February 1999, p. 958-964, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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