Viral takeover of the host ubiquitin system

Abstract

Like the other more well-characterized post-translational modifications (phosphorylation, methylation, acetylation, acylation, etc.), the attachment of the 76 amino acid ubiquitin (Ub) protein to substrates has been shown to govern countless cellular processes. As obligate intracellular parasites, viruses have evolved the capability to commandeer many host processes in order to maximize their own survival, whether it be to increase viral production or to ensure the long-term survival of latently infected host cells. The first evidence that viruses could usurp the Ub system came from the DNA tumor viruses and Adenoviruses, each of which use Ub to dysregulate the host cell cycle (Scheffner et al., 1990; Querido et al., 2001). Today, the list of viruses that utilize Ub includes members from almost every viral class, encompassing both RNA and DNA viruses. Among these, there are examples of Ub usage at every stage of the viral life cycle, involving both ubiquitination and de-ubiquitination. In addition to viruses that merely modify the host Ub system, many of the large DNA viruses encode their own Ub modifying machinery. In this review, we highlight the latest discoveries regarding the myriad ways that viruses utilize Ub to their advantage.

Keywords: proteasome; ubiquitin; ubiquitin ligase complex; ubiquitin proteasome system; viral lifecycle; virus.

Figure 1

A schematic overview depicting examples of viral interference with the host ubiquitin system. Included here are cases in which either the E3 ligases or specific targets are known. With the exception of the cellular DUBs shown in green, the Cullin proteins shown in purple, and the various Cullin complex members shown in gold, cellular proteins are shown in blue. All viral proteins are shown in red. Ub, ubiquitin. The box at the top contains the relatively few cases in which HECT ligases are utilized. The remainder of the examples shown depend upon RING-family ligases. In the majority of cases shown, ubiquitination leads to degradation of the target protein. When degradation is not the outcome, or when ubiquitination of normal targets is prevented, the resulting phenotype has been annotated. See main text for specific references.