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J. Virol. doi:10.1128/JVI.02032-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Evidence for differential roles for NKG2D signaling in innate host defense against coronavirus-induced neurological and liver disease

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

^* To whom correspondence should be addressed. Email: tlane{at}uci.edu.

	Abstract

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 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 IFN- 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. Administration of an NKG2D blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN- 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- expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D, and iii) NKG2D signaling promotes anti-viral activity within the livers of MHV-infected mice that is not dependent on IFN- and TNF- secretion.

This article has been cited by other articles:

• Walsh, K. B., Lanier, L. L., Lane, T. E. (2008). NKG2D Receptor Signaling Enhances Cytolytic Activity by Virus-Specific CD8+ T Cells: Evidence for a Protective Role in Virus-Induced Encephalitis. J. Virol. 82: 3031-3044 [Abstract] [Full Text]