THE HCMV GENE-PRODUCTS US11 AND US2 DIFFER IN THEIR ABILITY TO ATTACKALLELIC FORMS OF MURINE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-I HEAVY-CHAINS

Human cytomegalovirus downregulates the expression of human class I ma jor histocompatibility complex (MHC) molecules by accelerating destruc tion of newly synthesized class I heavy chains. The HCMV genome contai ns at least two genes, US11 and US2, each of which encode a product su fficient for causing the dislocation of newly synthesized class I heav y chains from the lumen of the endoplasmic reticulum to the cytosol. B ased on a comparison of their abilities to degrade the murine class I molecules H-2K(b), K-d, D-b, D-d, and L(d), the US11 and US2 gene prod ucts have non-identical specificities for class I molecules. Specifica lly, in human astrocytoma cells (U373-MG) transfected with the US11 ge ne, the K-b, D-b, D-d, and L(d) molecules expressed via recombinant va ccinia virus are rapidly degraded, whereas in US2-transfected cells, o nly D-b and D-d 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.