Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs.
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ICR Authors
Authors
Mihalič, F
Simonetti, L
Giudice, G
Sander, MR
Lindqvist, R
Peters, MBA
Benz, C
Kassa, E
Badgujar, D
Inturi, R
Ali, M
Krystkowiak, I
Sayadi, A
Andersson, E
Aronsson, H
Söderberg, O
Dobritzsch, D
Petsalaki, E
Överby, AK
Jemth, P
Davey, NE
Ivarsson, Y
Simonetti, L
Giudice, G
Sander, MR
Lindqvist, R
Peters, MBA
Benz, C
Kassa, E
Badgujar, D
Inturi, R
Ali, M
Krystkowiak, I
Sayadi, A
Andersson, E
Aronsson, H
Söderberg, O
Dobritzsch, D
Petsalaki, E
Överby, AK
Jemth, P
Davey, NE
Ivarsson, Y
Document Type
Journal Article
Date
2023-04-26
Date Accepted
2023-04-12
Abstract
Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery of 1712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses. We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry. Using structural and biophysical analyses, we show that viral mimicry-based interactions have similar binding strength and bound conformations as endogenous interactions. Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development. Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.
Citation
Nature Communications, 2023, 14 (1), pp. 2409 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Short Linear Motif