A viral ER-resident glycoprotein inactivates the MHC-encoded peptide transporter.
Human cytomegalovirus inhibits peptide import into the endoplasmic reticulum (ER) by the MHC-encoded TAP peptide transporter. We identified the open reading frame US6 to mediate this effect. Expression of the 21 kDa US6 glycoprotein in human cytomegalovirus-infected cells correlates with the inhibition of peptide transport during infection. The subcellular localization of US6 is ER restricted and is identical with TAP. US6 protein is found in complexes with TAP1/2, MHC class I heavy chain, beta2-microglobulin, calnexin, calreticulin, and tapasin. TAP inhibition, however, is independent of the presence of class I heavy chain and tapasin. The results establish a new mechanism for viral immune escape and a novel role for ER-resident proteins to regulate TAP via its luminal face.
Hengel
H
H
Max von Pettenkofer-Institut, Lehrstuhl Virologie, Genzentrum der Ludwig-Maximilians-Universität München, Germany.
Koopmann
J O
JO
Flohr
T
T
Muranyi
W
W
Goulmy
E
E
Hämmerling
G J
GJ
Koszinowski
U H
UH
Momburg
F
F
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017951:Antigen Presentation / Q000235:genetics; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism / Q000821:virology*; D006023:Glycoproteins / Q000096:biosynthesis / Q000494:pharmacology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis / Q000494:pharmacology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016601:RNA-Binding Proteins; C073119:TAP1 protein, human; D014764:Viral Proteins