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Journal of Virology, September 2005, p. 11335-11342, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11335-11342.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific Protein Enhances Virulence of an Attenuated Murine Coronavirus

Lecia Pewe,1,{dagger} Haixia Zhou,2,{dagger} Jason Netland,1 Chandra Tangudu,3 Heidi Olivares,3 Lei Shi,4 Dwight Look,4 Thomas Gallagher,3 and Stanley Perlman1,2*

Departments of Pediatrics,1 Microbiology,2 Internal Medicine, University of Iowa, Iowa City, Iowa 52242,4 Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois 601533

Received 11 April 2005/ Accepted 8 June 2005

Most animal species that can be infected with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) do not reproducibly develop clinical disease, hindering studies of pathogenesis. To develop an alternative system for the study of SARS-CoV, we introduced individual SARS-CoV genes (open reading frames [ORFs]) into the genome of an attenuated murine coronavirus. One protein, the product of SARS-CoV ORF6, converted a sublethal infection to a uniformly lethal encephalitis and enhanced virus growth in tissue culture cells, indicating that SARS-CoV proteins function in the context of a heterologous coronavirus infection. Furthermore, these results suggest that the attenuated murine coronavirus lacks a virulence gene residing in SARS-CoV. Recombinant murine coronaviruses cause a reproducible and well-characterized clinical disease, offer virtually no risk to laboratory personnel, and should be useful for elucidating the role of SARS-CoV nonstructural proteins in viral replication and pathogenesis.

* Corresponding author. Mailing address: Department of Pediatrics, University of Iowa, Medical Laboratories 2042, Iowa City, IA 52242. Phone: (319) 335-8549. Fax: (319) 335-8991. E-mail: Stanley-Perlman{at}uiowa.edu.

{dagger} L.P. and H.Z. contributed equally to the work.

Journal of Virology, September 2005, p. 11335-11342, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11335-11342.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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