Herpes simplex virus turns off the TAP to evade host immunity.
Many viruses have evolved mechanisms to avoid detection by the host immune system. Herpes simplex virus (HSV) expresses an immediate early protein, ICP47, which blocks presentation of viral peptides to MHC class I-restricted cells. The properties of the newly synthesized class I molecules in HSV-infected cells resemble those of cell lines deficient in the transporter associated with antigen processing (TAP) in that class I molecules are retained in the endoplasmic reticulum, and the heavy chain and beta 2-microglobulin subunits dissociate in detergent extracts but the complex can be stabilized by peptides. We show here that ICP47 binds to TAP and prevents peptide translocation into the endoplasmic reticulum.
Hill
A
A
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139-4307, USA.
Jugovic
P
P
York
I
I
Russ
G
G
Bennink
J
J
Yewdell
J
J
Ploegh
H
H
Johnson
D
D
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001692:Biological Transport; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007109:Immunity; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D018139:Simplexvirus / Q000276:immunology* / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C071692:TAP2 protein, human; D007371:Interferon-gamma; D000255:Adenosine Triphosphate