Forced association of SARS-CoV-2 proteins with the yeast proteome perturb vesicle trafficking
Authors:Cinzia Klemm1,#, Henry Wood1,#, Grace Heredge Thomas1,#, Guðjón Ólafsson1,2, Mara Teixeira Torres1 and Peter H. Thorpe1
doi: 10.15698/mic2021.12.766
Volume 8, pp. 280 to 296, published 27/10/2021.
1 School of Biological and Behavioural Sciences, Queen Mary University of London, E1 4NS, UK.
2 Institute for Systems Genetics, NYU Langone Health, New York, NY 10016, USA.
# Authors have contributed equally.
Keywords:
SARS-CoV-2, COVID-19, synthetic physical interactions, vesicle trafficking, transcription.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflicts of interest.
Please cite this article as:
Cinzia Klemm, Henry Wood, Grace Heredge Thomas, Guðjón Ólafsson, Mara Teixeira Torres and Peter H. Thorpe (2021). Forced association of SARS-CoV-2 proteins with the yeast proteome perturb vesicle trafficking. Microbial Cell 8(12): 280-296. doi: 10.15698/mic2021.12.766
© 2021 Klemm et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly infectious coronavirus disease COVID-19. Extensive research has been performed in recent months to better understand how SARS-CoV-2 infects and manipulates its host to identify potential drug targets and support patient recovery from COVID-19. However, the function of many SARS-CoV-2 proteins remains uncharacterised. Here we used the Synthetic Physical Interactions (SPI) method to recruit SARS-CoV-2 proteins to most of the budding yeast proteome to identify conserved pathways which are affected by SARS-CoV-2 proteins. The set of yeast proteins that result in growth defects when associated with the viral proteins have homologous functions that overlap those identified in studies performed in mammalian cells. Specifically, we were able to show that recruiting the SARS-CoV-2 NSP1 protein to HOPS, a vesicle-docking complex, is sufficient to perturb membrane trafficking in yeast consistent with the hijacking of the endoplasmic-reticulum–Golgi intermediate compartment trafficking pathway during viral infection of mammalian cells. These data demonstrate that the yeast SPI method is a rapid way to identify potential functions of ectopic viral proteins.