Please use this identifier to cite or link to this item: https://covid-19.conacyt.mx/jspui/handle/1000/1617
Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling
V'kovski, P
Gerber, M
Kelly, J
Pfaender, S
Ebert, N
Braga Lagache, S
Simillion, C
Portmann, J
Stalder, H
Gaschen, V
Bruggmann, R
Stoffel, M
Heller, M
Dijkman, R
Thiel, V
Acceso Abierto
Atribución-NoComercial-SinDerivadas
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 autophagy-related 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.
ELife
2019
Preimpreso
https://coronavirus.1science.com/item/742dc7711e8b4b3138c13daab2ff8c8ae2d66df2
Inglés
VIRUS RESPIRATORIOS
Appears in Collections:Artículos científicos

Upload archives


File SizeFormat 
110731.pdf5.92 MBAdobe PDFView/Open