The HCMV gene products US2 and US11 target MHC class I molecules for degradation in the cytosol.

Over millions of years of coevolution with their hosts, viruses have developed highly effective strategies to elude the host immune system. The degradation of major histocompatibility complex (MHC) class I heavy chains by human cytomegalovirus (HCMV) is an example of this. Two HCMV proteins, US2 and US11, target newly synthesized MHC class I heavy chains for destruction via a pathway that involves ubiquitin-dependent retrograde transport, or "dislocation", of the heavy chains from the ER to the cytosol, where the proteins are degraded by proteasomes. In this review, US2- and US11-mediated degradation of MHC class I heavy chains is discussed in relation to data concerning the degradation of other ER luminal proteins. A new, unified model for translocon-facilitated dislocation and degradation of MHC class I heavy chains is presented.