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Review
. 2021 Apr 23;22(9):4438.
doi: 10.3390/ijms22094438.

Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

Jessica Proulx  1 , Kathleen Borgmann  1 , In-Woo Park  2
Affiliations
Review

Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

Jessica Proulx et al. Int J Mol Sci. .

Abstract

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication.

Keywords: deubiquitinases (DUBs); ubiquitin proteasome system; ubiquitination; viruses.

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Conflict of interest statement

All authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1
Deubiquitination counteracts ubiquitination within the UPS by cleaving the peptide or isopeptide bond between Ub and its substrate proteins as well as between Ub molecules in a chain to reverse the fate of the ubiquitinated proteins. Viruses utilize DUBs to evade host immune response and expedite their survival. DUB pathways are illustrated by red arrows. Dotted lines denote Ub recycling. Blue text indicates ‘protein fate’ which coordinates outcomes that are regulated by the Ub system during host–viral interactions (blue box). Image made with BioRender.com.
Figure 2
Figure 2
Viruses block innate immune signaling pathways using DUB activity. Viral recognition (red) initiates a cascade of signaling mediators (purple/blue/turquoise) leading to the activation of transcription factors (green) to induce expression of proinflammatory cytokines and type I interferons (green boxes). Viruses (blue boxes) exploit virally encoded DUBs to block different steps within innate immune signaling pathways. Image made with BioRender.com.
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