After successful loading with antigenic peptide and survival of the ER quality control, the MHC class I molecules must go on to the plasma membrane in order to be reconized by cytotoxic lymphocytes.
Many viruses “intercept” the loaded MHC class I molecules and either retain it in the endoplasmic reticulum or target it to degradation in order to avoid presentation of the peptides at the cell surface. US2 and US11 of HCMV and mK3 form mouse herpesvirus 68 target human MHC class I molecules for degradation through the ERAD pathway. Other viral proteins including U21 from HHV-7 and m06 from MCMV mediate targeting of MHC molecules to the lysosomes and subsequent degradation. VZV ORF66 downregulates MHC I expression by impairing the transport of MHC I molecules from the Golgi compartment to the cell surface.