Down-regulation of the NKG2D ligand MICA by the human cytomegalovirus glycoprotein UL142.
Human cytomegalovirus (HCMV) employs a variety of strategies to modify or evade the host immune response, and natural killer (NK) cells play a crucial role in controlling cytomegalovirus infections in mice and humans. Activation of NK cells through the receptor NKG2D/DAP10 leads to killing of NKG2D ligand-expressing cells. We have previously shown that HCMV is able to down-regulate the surface expression of some NKG2D ligands, ULBP1, ULBP2, and MICB via the viral glycoprotein UL16. Here, we show that the viral gene product UL142 is able to down-regulate another NKG2D ligand, MICA, leading to protection from NK cytotoxicity. UL142 is not able to affect surface expression of all MICA alleles, however, which may reflect selective pressure on the host to thwart viral immune evasion, further supporting an important role for the MICA-NKG2D interaction in immune surveillance.
Chalupny
N Jan
NJ
Amgen, 1201 Amgen Court West, Seattle, WA 98119-3105, USA. chalupnj@amgen.com
Rein-Weston
Annie
A
Dosch
Stephanie
S
Cosman
David
D
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000276:immunology; D015536:Down-Regulation; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007694:Killer Cells, Natural; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D016415:Sequence Alignment; D014764:Viral Proteins / Q000096:biosynthesis / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C512704:UL142 protein, human herpesvirus 5; D014764:Viral Proteins