Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

Immunity to pathogens consists of innate and acquired responses that collectively block or diminish infections and usually leads to resolution of acute disease. Upon first exposure to a new pathogen the innate responses, primarily mediated through induction of interferon and cytokines, are a critical initial defense that dampens pathogen growth until pathogen-specific antibodies and T-cells are developed [46] . The innate response is triggered by recognition of pathogen-specific molecules by the Toll-like receptor (TLR) system which then initiates a signaling cascade that activates IRFs 3, 5, and 7 via phosphorylation; the activated IRFs turn on interferon transcription. Two of the TLRs, RIG-1 [47] and MDA5 [48] , and an adaptor protein in the TLR signaling pathway known as Pellino-1 [49] have recently been shown to be sumoylated proteins. Sumoylation of RIG-1 enhanced its association with Cardif and led to increased expression of interferon β. Likewise, MDA5 sumoylation also increased interferon production, indicating that sumoylation is a positive regulator of these two TLR pathways and possibly other TLRs. For both MDA5 and RIG-1, sumoylation and the subsequent increased interferon production repressed viral replication, while reducing overall sumoylation led to increased viral replication. These results suggest that viral down regulation of sumoylation would be beneficial to avoid triggering a strong innate response.