To TRIM or not to TRIM: the balance of host-virus interactions mediated by the ubiquitin system

Adam Hage, Ricardo Rajsbaum

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


The innate immune system responds rapidly to protect against viral infections, but an overactive response can cause harmful damage. To avoid this, the response is tightly regulated by post-translational modifications (PTMs). The ubiquitin system represents a powerful PTM machinery that allows for the reversible linkage of ubiquitin to activate and deactivate a target's function. A precise enzymatic cascade of ubiquitin-activating, conjugating and ligating enzymes facilitates ubiquitination. Viruses have evolved to take advantage of the ubiquitin pathway either by targeting factors to dampen the antiviral response or by hijacking the system to enhance their replication. The tripartite motif (TRIM) family of E3 ubiquitin ligases has garnered attention as a major contributor to innate immunity. Many TRIM family members limit viruses either indirectly as components in innate immune signalling, or directly by targeting viral proteins for degradation. In spite of this, TRIMs and other ubiquitin ligases can be appropriated by viruses and repurposed as valuable tools in viral replication. This duality of function suggests a new frontier of research for TRIMs and raises new challenges for discerning the subtleties of these pro-viral mechanisms. Here, we review current findings regarding the involvement of TRIMs in host-virus interactions. We examine ongoing developments in the field, including novel roles for unanchored ubiquitin in innate immunity, the direct involvement of ubiquitin ligases in promoting viral replication, recent controversies on the role of ubiquitin and TRIM25 in activation of the pattern recognition receptor RIG-I, and we discuss the implications these studies have on future research directions.

Original languageEnglish (US)
Pages (from-to)1641-1662
Number of pages22
JournalThe Journal of general virology
Issue number12
StatePublished - Dec 1 2019


  • E3 ubiquitin ligase
  • innate immunity
  • tripartite motif (TRIM)
  • ubiquitin
  • unanchored polyubiquitin
  • virus infection

ASJC Scopus subject areas

  • Virology


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