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

Mariska Van Huizen,Marjolein Kikkert

doi:10.3389/fcell.2019.00392

Abstract

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.

Highlights

Virus infection triggers an immediate response in the host cell, termed the innate immune response
The first evidence for this came from a study by Arimoto et al (2010). They showed that E3 ligase TRIM23 can conjugate K27-linked chains to NFκB essential modulator (NEMO) and that this is required for the induction of nuclear factor κB (NFκB) and IRF3 upon activation of RLR signaling (Arimoto et al, 2010)
NEMO interacts with the K27-linked chains conjugated to TRIM26, which induces the expression of proinflammatory cytokines, type I IFNs, and interferon stimulated genes (ISGs) (Ran et al, 2016)

Summary

Introduction

Virus infection triggers an immediate response in the host cell, termed the innate immune response. Interaction of MAVS with these chains results in a disruption of the MAVS signalosome and downstream IRF3 activation, thereby inhibiting the type I IFN response. Recruits TBK1 to STING and induces IRF3 activation and the production of type I IFNs and proinflammatory cytokines.

Results

Conclusion