The HCMV gene products US11 and US2 differ in their ability to attack allelic forms of murine major histocompatibility complex (MHC) class I heavy chains.
Human cytomegalovirus downregulates the expression of human class I major histocompatibility complex (MHC) molecules by accelerating destruction of newly synthesized class I heavy chains. The HCMV genome contains at least two genes, US11 and US2, each of which encode a product sufficient for causing the dislocation of newly synthesized class I heavy chains from the lumen of the endoplasmic reticulum to the cytosol. Based on a comparison of their abilities to degrade the murine class I molecules H-2Kb, Kd, Db, Dd, and Ld, the US11 and US2 gene products have non-identical specificities for class I molecules. Specifically, in human astrocytoma cells (U373-MG) transfected with the US11 gene, the Kb, Db, Dd, and Ld molecules expressed via recombinant vaccinia virus are rapidly degraded, whereas in US2-transfected cells, only Db and Dd are significantly destabilized. The diversity in HCMV-encoded functions that interfere with class I-restricted presentation likely evolved in response to the polymorphism of the MHC.
Machold
R P
RP
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Wiertz
E J
EJ
Jones
T R
TR
Ploegh
H L
HL
D000483:Alleles; D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics*; D006031:Glycosylation; D006183:H-2 Antigens / Q000378:metabolism; D006868:Hydrolysis; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins