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J. Virol. doi:10.1128/JVI.02406-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Severe Acute Respiratory Syndrome Coronavirus Protein 6 Accelerates MHV Infections by More Than one Mechanism

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

^* To whom correspondence should be addressed. Email: tgallag{at}lumc.edu.

	Abstract

The 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 report, 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 pre-existing 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 siRNAs directed against importin-beta 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 were clearly not the only way that this accessory protein operated to create a milieu conducive to robust virus growth. Thus the SARS-CoV protein 6 accelerates MHV infections by more than one mechanism.