Model for US2 action in HCMV-infected cells.

<p>US2 targets a wide variety of novel cell surface substrates, including integrins, the NK cell ligand CD112, the anti-coagulation factor thrombomodulin and the IL-12 receptor β 1. The majority of these targets are directly targeted for proteasomal degradation in a TRC8 E3 ligase dependent pathway. β1 integrin is not itself degraded, but accumulates in an ER-resident immature form following US2-induced degradation of its α integrin interaction partner. CD112 is retained in the ER by UL141 from where US2 promotes the TRC8-dependent degradation. The functional consequences of US2 substrate degradation include diminished cell adhesion, migration, NK cell activation and antigen presentation.