Proteomic Approaches to Dissect Host SUMOylation during Innate Antiviral Immune Responses

Abstract

SUMOylation is a highly dynamic ubiquitin-like post-translational modification that is essential for cells to respond to and resolve various genotoxic and proteotoxic stresses. Virus infections also constitute a considerable stress scenario for cells, and recent research has started to uncover the diverse roles of SUMOylation in regulating virus replication, not least by impacting antiviral defenses. Here, we review some of the key findings of this virus-host interplay, and discuss the increasingly important contribution that large-scale, unbiased, proteomic methodologies are making to discoveries in this field. We highlight the latest proteomic technologies that have been specifically developed to understand SUMOylation dynamics in response to cellular stresses, and comment on how these techniques might be best applied to dissect the biology of SUMOylation during innate immunity. Furthermore, we showcase a selection of studies that have already used SUMO proteomics to reveal novel aspects of host innate defense against viruses, such as functional cross-talk between SUMO proteins and other ubiquitin-like modifiers, viral antagonism of SUMO-modified antiviral restriction factors, and an infection-triggered SUMO-switch that releases endogenous retroelement RNAs to stimulate antiviral interferon responses. Future research in this area has the potential to provide new and diverse mechanistic insights into host immune defenses.

Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy

“…Notably, SUMOylation is a post-translational modification regulating numerous cellular processes 21 . During viral infection, SUMOmediated regulation is involved in the virus replication and host type I interferon responses [53][54][55] . Our study indicated that treatment with global SUMOylation inhibitors resulted in the destabilization of ACE2 and the reduced SARS-CoV-2 infection in cells.…”

SUMOylation of Nuclear γ-Actin by SUMO2 supports DNA Damage Repair against Myocardial Ischemia-Reperfusion Injury

“…The present study was designed to identify SUMO2modified proteins and elucidate the cardioprotective mechanisms. SUMOylated proteins were successfully isolated by several strategies including SUMO antibody, an N-terminal tandem affinity protein tag, N-6xHis-SUMO transfection and GST-SIM fusion protein [42][43][44]. In the present study, we introduced the plasmid construct pcDNA3.…”