Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs
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-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38015-5 |
| _version_ | 1827956708082712576 |
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| author | Filip Mihalič Leandro Simonetti Girolamo Giudice Marie Rubin Sander Richard Lindqvist Marie Berit Akpiroro Peters Caroline Benz Eszter Kassa Dilip Badgujar Raviteja Inturi Muhammad Ali Izabella Krystkowiak Ahmed Sayadi Eva Andersson Hanna Aronsson Ola Söderberg Doreen Dobritzsch Evangelia Petsalaki Anna K. Överby Per Jemth Norman E. Davey Ylva Ivarsson |
| author_facet | Filip Mihalič Leandro Simonetti Girolamo Giudice Marie Rubin Sander Richard Lindqvist Marie Berit Akpiroro Peters Caroline Benz Eszter Kassa Dilip Badgujar Raviteja Inturi Muhammad Ali Izabella Krystkowiak Ahmed Sayadi Eva Andersson Hanna Aronsson Ola Söderberg Doreen Dobritzsch Evangelia Petsalaki Anna K. Överby Per Jemth Norman E. Davey Ylva Ivarsson |
| author_sort | Filip Mihalič |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:09:03Z |
| format | Article |
| id | doaj.art-e64e95cb96fe4ac196aaf0a9198064f8 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T15:09:03Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e64e95cb96fe4ac196aaf0a9198064f82023-04-30T11:21:49ZengNature PortfolioNature Communications2041-17232023-04-0114112010.1038/s41467-023-38015-5Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifsFilip Mihalič0Leandro Simonetti1Girolamo Giudice2Marie Rubin Sander3Richard Lindqvist4Marie Berit Akpiroro Peters5Caroline Benz6Eszter Kassa7Dilip Badgujar8Raviteja Inturi9Muhammad Ali10Izabella Krystkowiak11Ahmed Sayadi12Eva Andersson13Hanna Aronsson14Ola Söderberg15Doreen Dobritzsch16Evangelia Petsalaki17Anna K. Överby18Per Jemth19Norman E. Davey20Ylva Ivarsson21Department of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Chemistry - BMC, Uppsala UniversityEuropean Molecular Biology Laboratory-European Bioinformatics InstituteDepartment of Pharmaceutical Biosciences, Uppsala UniversityDepartment of Clinical Microbiology, Umeå UniversityDepartment of Clinical Microbiology, Umeå UniversityDepartment of Chemistry - BMC, Uppsala UniversityDepartment of Chemistry - BMC, Uppsala UniversityDepartment of Chemistry - BMC, Uppsala UniversityDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Chemistry - BMC, Uppsala UniversityDivision of Cancer Biology, The Institute of Cancer ResearchDepartment of Chemistry - BMC, Uppsala UniversityDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Pharmaceutical Biosciences, Uppsala UniversityDepartment of Chemistry - BMC, Uppsala UniversityEuropean Molecular Biology Laboratory-European Bioinformatics InstituteDepartment of Clinical Microbiology, Umeå UniversityDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityDivision of Cancer Biology, The Institute of Cancer ResearchDepartment of Chemistry - BMC, Uppsala UniversityAbstract 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.https://doi.org/10.1038/s41467-023-38015-5 |
| spellingShingle | Filip Mihalič Leandro Simonetti Girolamo Giudice Marie Rubin Sander Richard Lindqvist Marie Berit Akpiroro Peters Caroline Benz Eszter Kassa Dilip Badgujar Raviteja Inturi Muhammad Ali Izabella Krystkowiak Ahmed Sayadi Eva Andersson Hanna Aronsson Ola Söderberg Doreen Dobritzsch Evangelia Petsalaki Anna K. Överby Per Jemth Norman E. Davey Ylva Ivarsson Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs Nature Communications |
| title | Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs |
| title_full | Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs |
| title_fullStr | Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs |
| title_full_unstemmed | Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs |
| title_short | Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs |
| title_sort | large scale phage based screening reveals extensive pan viral mimicry of host short linear motifs |
| url | https://doi.org/10.1038/s41467-023-38015-5 |
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