Ubiquitination mediates protein localization in RNA virus-infected cells

Abstract

AbstractViruses trigger monocytes’ proinflammatory and antiviral responses. Ubiquitination, a post-translational modification primarily marking proteins for degradation, regulates cellular responses to virus infection. However, a comprehensive analysis of virus-induced ubiquitination in monocytes is lacking. Here we identified a widespread increase of ubiquitination under viral RNA challenge or influenza infection in monocytes. Systematic proteome studies revealed that influenza infection elicits dynamic ubiquitinome alterations, with a notable transition from early to late stage. Most of this increased ubiquitination is not proteolytic and targets proteins involved in subcellular localization, such as the mitochondrial protein COA7 which, when ubiquitinated during infection, translocates to the nucleus and inhibits stress granules formation and TNF-α expression. Blocking ubiquitination halts viral ribonucleoprotein’s nuclear export, highlighting ubiquitination’s importance for protein localization during virus infection.