Rabies virus P protein binds to TBK1 and interferes with the formation of innate immunity-related liquid condensates

• DOI: 10.1016/j.celrep.2022.111949
• Publication Date: 2023-01-05T03:40:40Z
• Authors: Nathalie Scrima; Romain Le Bars; Quentin Nevers; Damien Glon; Guillaume Chevreux; Ahmet Civas; Danielle Blondel; Cécile Lagaudrièr...; Yves Gaudin
• Keywords: TANK-binding kinase 1; IRF3; Phosphoprotein; Antiviral protein; RIG-I

Viruses must overcome the interferon-mediated antiviral response to replicate and propagate into their host. Rabies virus (RABV) phosphoprotein P is known inhibit interferon induction. Here, using a global mass spectrometry approach, we show that RABV binds TBK1, kinase located at crossroads of many induction pathways, resulting in innate immunity inhibition. Mutations TBK1 phosphorylation sites abolish binding. Importantly, demonstrate upon infection or detection dsRNA by sensors, its adaptor proteins NAP1 SINTBAD form dynamic cytoplasmic condensates have liquid properties. These can larger aggregates having ring-like structures which exhibit locally restricted movement. binding interferes with formation these structures. This work demonstrates signaling pathway leading transiently organelles be targeted viruses.