title: KSHV-K5 inhibits phosphorylation of the major histocompatibility complex class I cytoplasmic tail.
abstract: The carboxy-terminal region of major histocompatibility complex class I (MHC I) molecules is required for the rapid internalization mediated by Kaposi's sarcoma-associated herpesvirus (KSHV) proteins K3 and K5. The cytoplasmic tail of MHC I contains highly conserved serine phosphorylation sites that have been implicated in intracellular trafficking. Indeed, in vivo labeling experiments reveal a lack of MHC I phosphorylation in K5-transfected HeLa cells. Phosphorylation of the MHC I tail was restored upon mutation of the PHD/LAP domain of K5. However, deletion and mutation studies of the MHC I tail show that both K3 and K5 are able to downregulate MHC I lacking the conserved phosphorylation site. This result suggests that inhibition of phosphorylation reflects, but does not cause, MHC I internalization. Interestingly, K3 and K5 differ from each other, as well as from human immunodeficiency virus nef, with respect to the minimal MHC I tail sequences required for MHC downregulation. These data support the notion that K3 and K5 downregulate MHC I molecules by a distinct molecular mechanism that is different from other viral immune evasion molecules.
authors.affiliation: The R. W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego, California 92121, USA.
authors.forename: E
authors.initials: E
authors.lastname: Paulson
authors.forename: C
authors.initials: C
authors.lastname: Tran
authors.forename: K
authors.initials: K
authors.lastname: Collins
authors.forename: K
authors.initials: K
authors.lastname: Früh
mesh_terms: D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; C405867:K5 protein, Human herpesvirus 8