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Journal of Virology, March 2008, p. 3021-3030, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02032-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease{triangledown}

Kevin B. Walsh,1 Melissa B. Lodoen,3 Robert A. Edwards,2,4 Lewis L. Lanier,3 and Thomas E. Lane1,2*

Department of Molecular Biology & Biochemistry,1 Center for Immunology, University of California, Irvine, California 92697,2 Department of Microbiology & Immunology and Cancer Research Institute, University of California, San Francisco, California 94143,3 Department of Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, California 926974

Received 13 September 2007/ Accepted 13 December 2007

Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-{gamma}) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-{gamma} production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-{gamma} expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-{gamma} and tumor necrosis factor alpha secretion.

* Corresponding author. Mailing address: Department of Molecular Biology & Biochemistry, 3205 McGaugh Hall, University of California, Irvine, Irvine, CA 92697-3900. Phone: (949) 824-5878. Fax: (949) 824-8551. E-mail: tlane{at}uci.edu

{triangledown} Published ahead of print on 19 December 2007.

Journal of Virology, March 2008, p. 3021-3030, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02032-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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  • Thirion, G., Coutelier, J.-P. (2009). Production of protective gamma interferon by natural killer cells during early mouse hepatitis virus infection. J. Gen. Virol. 90: 442-447 [Abstract] [Full Text]  
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