Virus subversion of the MHC class I peptide-loading complex.
Many viral proteins modulate class I expression, yet, in general, their mechanisms of specific class I recognition are poorly understood. The mK3 protein of gamma(2)-Herpesvirus 68 targets the degradation of nascent class I molecules via the ubiquitin/proteasome pathway. Here, we identify cellular components of the MHC class I assembly machinery, TAP and tapasin, that are required for mK3 function. mK3 failed to regulate class I in TAP- or tapasin-deficient cells, and mK3 interacted with TAP/tapasin, even in the absence of class I. Expression of mK3 resulted in the ubiquitination of TAP/tapasin-associated class I, and mutants of class I incapable of TAP/tapasin interaction were unaffected by mK3. Thus, mK3 subverts TAP/tapasin to specifically target class I molecules for destruction.
Lybarger
Lonnie
L
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wang
Xiaoli
X
Harris
Michael R
MR
Virgin
Herbert W
HW
Hansen
Ted H
TH
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D017920:Antiporters / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D018142:Gammaherpesvirinae / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity; D018390:Gene Targeting; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D009154:Mutation; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / 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; D017920:Antiporters; D037282:Calreticulin; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; D014764:Viral Proteins; D001613:beta 2-Microglobulin; C107762:tapasin; C071692:TAP2 protein, human