{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:00:39Z","timestamp":1791558039194,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011535","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171421, AI137471, AI169460"],"award-info":[{"award-number":["AI171421, AI137471, AI169460"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI127447"],"award-info":[{"award-number":["AI127447"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We identify specific translation factors and molecular chaperones that are used by CoV2 to promote the synthesis and maturation of its own proteins. These can be targeted to inhibit infection, without major toxicity to the host. We also find that CoV2 non-structural protein 1 (Nsp1) cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA. When EIF1\/1A are depleted, more ribosomes initiate translation from a conserved upstream CUG start codon found in all genomic and subgenomic viral RNAs. This results in higher translation of an upstream open reading frame (uORF1) and lower translation of the main ORF, altering the stoichiometry of viral proteins and attenuating infection. Replacing the upstream CUG with AUG strongly inhibits translation of the main ORF independently of Nsp1, EIF1, or EIF1A. Taken together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and proposes a model for dosage control of viral proteins through Nsp1-mediated control of translation start site selection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011535","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T18:34:58Z","timestamp":1707503698000},"page":"e1011535","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA"],"prefix":"10.1371","volume":"20","author":[{"given":"Ranen","family":"Aviner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter 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V\u2019kovski","year":"2019","journal-title":"Elife"},{"key":"ppat.1011535.ref025","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/s41594-020-0511-8","article-title":"SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation","volume":"27","author":"K Schubert","year":"2020","journal-title":"Nat Struct Mol Biol"},{"key":"ppat.1011535.ref026","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1261\/rna.079086.121","article-title":"The key features of SARS-CoV-2 leader and NSP1 required for viral escape of NSP1-mediated repression","volume":"28","author":"L Bujanic","year":"2022","journal-title":"RNA"},{"key":"ppat.1011535.ref027","doi-asserted-by":"crossref","first-page":"8080","DOI":"10.1093\/nar\/gkac615","article-title":"Cap-independent translation and a precisely located RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response","volume":"50","author":"B Slobodin","year":"2022","journal-title":"Nucleic Acids 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She","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011535.ref053","doi-asserted-by":"crossref","first-page":"e1002137","DOI":"10.1371\/journal.pgen.1002137","article-title":"Translation Reinitiation Relies on the Interaction between eIF3a\/TIF32 and Progressively Folded cis-Acting mRNA Elements Preceding Short uORFs.","volume":"7","author":"V Munzarov\u00e1","year":"2011","journal-title":"PLoS Genet."},{"key":"ppat.1011535.ref054","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1101\/gad.480508","article-title":"eIF3a cooperates with sequences 5\u2032 of uORF1 to promote resumption of scanning by post-termination ribosomes for reinitiation on GCN4 mRNA","volume":"22","author":"B Szamecz","year":"2008","journal-title":"Genes Dev"},{"key":"ppat.1011535.ref055","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1093\/nar\/gkab287","article-title":"DDX3 depletion represses translation of mRNAs with complex 5\u2032 UTRs","volume":"49","author":"L 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