Hantavirus Regulation of Type I Interferon Responses

Figure 1

Potential model of hantavirus Gn-T disruption of STING-TBK1-IRF3 complex formation. Normally RIG-I/Mda5 recognition of viral RNA activates mitochondrial MAVS resulting in the downstream activation, phosphorylation, and dimerization of ER-resident STING [59–62, 65, 80]. STING is a scaffolding protein that binds TBK1 complexes through its C-terminal cytoplasmic domain [60, 61, 65], and STING-recruited TBK1 phosphorylates IRF3 and IκB. This activates NF-κB, permits IRF3 dimerization, and results in nuclear translocation of both IRF3 and NF-κB which are both required for IFNβ transcription. Expression of the NY-1V, ANDV, or TULV Gn-T inhibits RIG-I- and TBK1-directed IFNβ transcription but has no effect on activated IRF3 [49–51]. Gn-T expression disrupts TBK1 binding to TRAF3 and acts at the level of STING-TBK1 complex formation to inhibit IRF3 and NF-κB activation [49–51]. The specific interactions of the Gn-T with STING and TBK1 complexes that inhibit downstream pathway activation remain to be defined.