TY - JOUR
T1 - KSHV-K5 inhibits phosphorylation of the major histocompatibility complex class I cytoplasmic tail
AU - Paulson, Emily
AU - Tran, Chinh
AU - Collins, Kathleen
AU - Früh, Klaus
PY - 2001/9/30
Y1 - 2001/9/30
N2 - 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.
AB - 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.
KW - HHV8
KW - Immune escape
KW - Intracellular transport
KW - KSHV
KW - Kaposi's sarcoma
KW - Major histocompatibility complex class I
KW - Serine phosphorylation
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UR - http://www.scopus.com/inward/citedby.url?scp=0035975641&partnerID=8YFLogxK
U2 - 10.1006/viro.2001.1086
DO - 10.1006/viro.2001.1086
M3 - Article
C2 - 11601908
AN - SCOPUS:0035975641
SN - 0042-6822
VL - 288
SP - 369
EP - 378
JO - Virology
JF - Virology
IS - 2
ER -