FIG. 9.

Proposed model of the ubiquitin-proteasome pathway in MHC class I downregulation by KSHV K3. (Step 1) MHC class I complexes are internalized from the plasma membrane in K3-expressing cells in a step independent of the ubiquitin-proteasome pathway. (Step 2) Active proteasomes and/or the levels of ubiquitin (Ub) mediate sorting of MHC class I complexes from an early endocytic compartment to a late, dense endocytic compartment, most likely the multivesicular body. (Step 3) Once in this compartment, cysteine proteases remove the cytoplasmic tail of MHC class I HC, while aspartic proteases sequentially cleave MHC class I HC within the plane of the membrane (step 4). (Step 5) The soluble lumenal fragment of MHC class I is then delivered to lysosomes for complete degradation.