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Journal of Virology, July 2008, p. 7212-7222, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.02406-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates Murine Hepatitis Virus Infections by More than One Mechanism{triangledown}

Snawar Hussain,1 Stanley Perlman,2 and Thomas M. Gallagher1*

Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, Illinois,1 Interdisciplinary Program in Immunology, Department of Microbiology, University of Iowa, Iowa City, Iowa2

Received 7 November 2007/ Accepted 25 April 2008

The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes numerous accessory proteins whose importance in the natural infection process is currently unclear. One of these accessory proteins is set apart by its function in the context of a related murine hepatitis virus (MHV) infection. SARS-CoV protein 6 increases MHV neurovirulence and accelerates MHV infection kinetics in tissue culture. Protein 6 also blocks nuclear import of macromolecules from the cytoplasm, a process known to involve its C-terminal residues interacting with cellular importins. In this study, protein 6 was expressed from plasmid DNAs and accumulated in cells prior to infection by wild-type MHV. Output of MHV progeny was significantly increased by preexisting protein 6. Protein 6 with C-terminal deletion mutations no longer interfered with nuclear import processes but still retained much of the capacity to augment MHV infections. However, some virus growth-enhancing activity could be ascribed to the C-terminal end of protein 6. To determine whether this augmentation provided by the C terminus was derived from interference with nuclear import, we evaluated the virus-modulating effects of small interfering RNAs (siRNAs) directed against importin-β mRNAs, which down-regulated classical nuclear import pathways. The siRNAs did indeed prime cells for enhanced MHV infection. Our findings indicated that protein 6-mediated nuclear import blocks augmented MHV infections but is clearly not the only way that this accessory protein operates to create a milieu conducive to robust virus growth. Thus, the SARS-CoV protein 6 accelerates MHV infections by more than one mechanism.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153. Phone: (708) 216-4850. Fax: (708) 216-9574. E-mail: tgallag{at}lumc.edu

{triangledown} Published ahead of print on 30 April 2008.

Journal of Virology, July 2008, p. 7212-7222, Vol. 82, No. 14
0022-538X/08/$08.00+0     doi:10.1128/JVI.02406-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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