The Role of Atypical Ubiquitin Chains in the Regulation of the Antiviral Innate Immune Response

It is well established that polyubiquitin chains, in particular those linked through K48 and K63, play a key role in the regulation of the antiviral innate immune response. However, the role of the atypical chains linked via any of the other lysine residues (K6, K11, K27, K29, and K33) and the M1-linked linear chains have not been investigated very well yet in this context. This is partially due to a lack of tools to study these linkages in their biological context. Interestingly though, recent findings underscore the importance of the atypical chains in the regulation of the antiviral immune response. This review will highlight the most important advances in the study of the role of atypical ubiquitin chains, particularly in the regulation of intracellular antiviral innate immune signaling pathways. We will also discuss the development of new tools and how these can increase our knowledge of the role of atypical ubiquitin chains.