RT Journal Article
SR Electronic
T1 Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.28.272955
DO 10.1101/2020.08.28.272955
A1 Laurent, Estelle M.N.
A1 Sofianatos, Yorgos
A1 Komarova, Anastassia
A1 Gimeno, Jean-Pascal
A1 Tehrani, Payman Samavarchi
A1 Kim, Dae-Kyum
A1 Abdouni, Hala
A1 Duhamel, Marie
A1 Cassonnet, Patricia
A1 Knapp, Jennifer J.
A1 Kuang, Da
A1 Chawla, Aditya
A1 Sheykhkarimli, Dayag
A1 Rayhan, Ashyad
A1 Li, Roujia
A1 Pogoutse, Oxana
A1 Hill, David E.
A1 Calderwood, Michael A.
A1 Falter-Braun, Pascal
A1 Aloy, Patrick
A1 Stelzl, Ulrich
A1 Vidal, Marc
A1 Gingras, Anne-Claude
A1 Pavlopoulos, Georgios A.
A1 Van Der Werf, Sylvie
A1 Fournier, Isabelle
A1 Roth, Frederick P.
A1 Salzet, Michel
A1 Demeret, Caroline
A1 Jacob, Yves
A1 Coyaud, Etienne
YR 2020
UL http://biorxiv.org/content/early/2020/08/29/2020.08.28.272955.abstract
AB The worldwide SARS-CoV-2 outbreak poses a serious challenge to human societies and economies. SARS-CoV-2 proteins orchestrate complex pathogenic mechanisms that underlie COVID-19 disease. Thus, understanding how viral polypeptides rewire host protein networks enables better-founded therapeutic research. In complement to existing proteomic studies, in this study we define the first proximal interaction network of SARS-CoV-2 proteins, at the whole proteome level in human cells. Applying a proximity-dependent biotinylation (BioID)-based approach greatly expanded the current knowledge by detecting interactions within poorly soluble compartments, transient, and/or of weak affinity in living cells. Our BioID study was complemented by a stringent filtering and uncovered 2,128 unique cellular targets (1,717 not previously associated with SARS-CoV-1 or 2 proteins) connected to the N- and C-ter BioID-tagged 28 SARS-CoV-2 proteins by a total of 5,415 (5,236 new) proximal interactions. In order to facilitate data exploitation, an innovative interactive 3D web interface was developed to allow customized analysis and exploration of the landscape of interactions (accessible at http://www.sars-cov-2-interactome.org/). Interestingly, 342 membrane proteins including interferon and interleukin pathways factors, were associated with specific viral proteins. We uncovered ORF7a and ORF7b protein proximal partners that could be related to anosmia and ageusia symptoms. Moreover, comparing proximal interactomes in basal and infection-mimicking conditions (poly(I:C) treatment) allowed us to detect novel links with major antiviral response pathway components, such as ORF9b with MAVS and ISG20; N with PKR and TARB2; NSP2 with RIG-I and STAT1; NSP16 with PARP9-DTX3L. Altogether, our study provides an unprecedented comprehensive resource for understanding how SARS-CoV-2 proteins orchestrate host proteome remodeling and innate immune response evasion, which can inform development of targeted therapeutic strategies.Competing Interest StatementThe authors have declared no competing interest.