PubMed:18230726 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":46,"end":62},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":204,"end":220},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":392,"end":438},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":598,"end":602},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":1340,"end":1344},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0005055"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0005108"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0005055"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0005055"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0005055"}],"text":"Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity.\nNatural killer (NK) cells are important early mediators of host immunity to viral infections. The NK activatory receptors NKG2D and NKp80, both C-type lectin-like homodimeric receptors, stimulate NK cell cytotoxicity toward target cells. Like other herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV) down-regulates MHC class I molecules to avoid detection by cytotoxic T lymphocytes but renders cells susceptible to NK cell cytotoxicity. We now show that the KSHV immune evasion gene, K5, reduces cell surface expression of the NKG2D ligands MHC class I-related chain A (MICA), MICB, and the newly defined ligand for NKp80, activation-induced C-type lectin (AICL). Down-regulation of both MICA and AICL requires the ubiquitin E3 ligase activity of K5 to target substrate cytoplasmic tail lysine residues. The common MICA *008 allele has a frameshift mutation leading to a premature stop codon and is resistant to down-regulation because of the loss of lysine residues. K5-mediated ubiquitylation signals internalization but not degradation of MICA and causes a potent reduction in NK cell-mediated cytotoxicity. The down-regulation of ligands for both the NKG2D and NKp80 activation pathways provides KSHV with a powerful mechanism for evasion of NK cell antiviral functions."}