Ubiquitin in the activation and attenuation of innate antiviral immunity

Heaton, Steven M.; Borg, Natalie A.; Dixit, Vishva M.

Ubiquitin stringently regulates the MAVS signalosome. The central position that MAVS occupies within the RLR cascade is commensurate with the many PTMs that modulate its role. To our knowledge, MAVS ubiquitination has not been observed in resting cells using a variety of proteomic and biochemical approaches, indicating that MAVS ubiquitination occurs specifically during viral infection. At least seven E3s ubiquitinate MAVS, leading to MAVS degradation in almost every case, as described later in this section (Fig. 3) . At least five of these modify other substrates within the same cascade, highlighting MAVS as a crucial locus of RLR regulation. Accordingly, MAVS is targeted by numerous viruses in a variety of ways; however, with the exception of HBV and severe acute respiratory syndrome-coronavirus (SARS-CoV; Fig. 3 ; Wei et al., 2010; Shi et al., 2014) , this is usually achieved by means other than manipulating MAVS ubiquitination, likely given the extensive ubiquitin-mediated negative regulatory systems already in place.