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- Title
Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling.
- Authors
V'kovski, Philip; Gerber, Markus; Kelly, Jenna; Pfaender, Stephanie; Ebert, Nadine; Lagache, Sophie Braga; Simillion, Cedric; Portmann, Jasmine; Stalder, Hanspeter; Gaschen, Véronique; Bruggmann, Rémy; Stoffel, Michael H.; Heller, Manfred; Dijkman, Ronald; Thiel, Volker
- Abstract
Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagyrelated processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.
- Publication
eLife, 2019, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.42037.001