Numerous cellular processes are regulated by the reversible conjugation of ubiquitin (UB) or ubiquitin-like (UBL) proteins to substrates. Typically, a ubiquitin-activating enzyme (E1) binds ubiquitin in an adenosine triphosphate dependent manner. Ubiquitin is then transferred to a ubiquitin-conjugating enzyme (E2). A ubiquitin ligase (E3) helps transfer ubiquitin to the target substrate. In turn, polyubiquitination targets proteins to a cellular organelle known as the 26S proteasome where substrates are degraded into small peptides. Proteasomal degradation is critical component of many cellular processes including cell cycle regulation,induction of the inflammatory response and antigen presentation.
Viruses have evolved different strategies to modulate host cell ubiquitin machinery. The reasons of this manipulation are multiple including modulation of the host cell cycle, viral replication, inhibition of the host immune system or viral budding. The modification of the ub system includes the modulation of cellular E3 ligases, the synthesis of viral E3 ligases, viral deubiquitinases, or viral ubiquitin-like proteins that will perturb normal host Ub pathways.