NK cell receptors and their MHC class I ligands in host response to cytomegalovirus: Insights from the mouse genome

The complex interaction between natural killer (NK) cells and cytomegalovirus is a paradigm of the co-evolution between genomes of large DNA viruses and their host immune systems. Both human and mouse cytomegalovirus posses numerous mechanisms to avoid NK cell detection. Linkage studies, positional cloning and functional studies in mice and cells, have led to the identification of key genes governing resistance to cytomegalovirus, including various NK cell activating receptors of major histocompatibility complex (MHC) class I. These receptors, however, seem to require either viral or host MHC class I molecules to operate recognition and elimination of the cytomegalovirus-infected cell leading to host resistance. Here we will review the genes and molecules involved in these mechanisms while contrasting their function with that of other NK cell receptors. Activating receptors of MHC class I may represent a window of therapeutic intervention during human infection with viruses, of which cytomegalovirus remains an important health threat.