Cytomegalovirus evasion of innate immunity by subversion of the NKR-P1B:Clr-b missing-self axis
- PMID: 17462921
- DOI: 10.1016/j.immuni.2007.03.013
Cytomegalovirus evasion of innate immunity by subversion of the NKR-P1B:Clr-b missing-self axis
Abstract
Cytomegaloviruses are known to encode several gene products that function to subvert MHC-dependent immune recognition. Here we characterize a rat cytomegalovirus (RCMV) C-type lectin-like (RCTL) gene product with homology to the Clr ligands for the NKR-P1 receptors. RCMV infection rapidly extinguished host Clr-b expression, thereby sensitizing infected cells to killing by natural killer (NK) cells. However, the RCTL protein functioned as a decoy ligand to protect infected cells from NK killing via direct interaction with the NKR-P1B inhibitory receptor. In vivo, an RCTL mutant virus displayed diminished virulence in an NK-dependent and strain-specific manner, suggesting that host NKR-P1 polymorphisms have evolved to avert the viral decoy mechanism while maintaining Clr-b recognition to preserve self tolerance. These findings reveal a unique strategy adopted by cytomegaloviruses to evade MHC-independent self-nonself discrimination. The existence of lectin-like genes in several poxviruses suggests that this may represent a common theme for viral evasion of innate immunity.
Comment in
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Good news, bad news for missing-self recognition by NK cells: autoimmune control but viral evasion.Immunity. 2007 May;26(5):549-51. doi: 10.1016/j.immuni.2007.05.006. Immunity. 2007. PMID: 17521583
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