RGD Reference Report - Evidence for differential roles for NKG2D receptor signaling in innate host defense against coronavirus-induced neurological and liver disease. - Rat Genome Database

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

Authors: Walsh, Kevin B  Lodoen, Melissa B  Edwards, Robert A  Lanier, Lewis L  Lane, Thomas E 
Citation: Walsh KB, etal., J Virol. 2008 Mar;82(6):3021-30. doi: 10.1128/JVI.02032-07. Epub 2007 Dec 19.
RGD ID: 38676499
Pubmed: PMID:18094157   (View Abstract at PubMed)
PMCID: PMC2259007   (View Article at PubMed Central)
DOI: DOI:10.1128/JVI.02032-07   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Coronaviridae Infections  ISOKlrk1 (Mus musculus)38676499; 38676499 RGD 
Coronaviridae Infections  IMP 38676499 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klrk1  (killer cell lectin like receptor K1)

Genes (Mus musculus)
Klrk1  (killer cell lectin-like receptor subfamily K, member 1)

Genes (Homo sapiens)
KLRK1  (killer cell lectin like receptor K1)


Additional Information