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SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions

When viruses like SARS-CoV-2 infect cells, they reprogram the repertoire of cellular and viral transcripts that are being translated to optimize their strategy of replication, often targeting host translation initiation factors, particularly eIF4F complex consisting of eIF4E, eIF4G and eIF4A. A prot...

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Autores principales: Korneeva, Nadejda, Khalil, Md Imtiaz, Ghosh, Ishita, Fan, Ruping, Arnold, Thomas, De Benedetti, Arrigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060939/
https://www.ncbi.nlm.nih.gov/pubmed/36998012
http://dx.doi.org/10.1186/s12985-023-02021-2
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author Korneeva, Nadejda
Khalil, Md Imtiaz
Ghosh, Ishita
Fan, Ruping
Arnold, Thomas
De Benedetti, Arrigo
author_facet Korneeva, Nadejda
Khalil, Md Imtiaz
Ghosh, Ishita
Fan, Ruping
Arnold, Thomas
De Benedetti, Arrigo
author_sort Korneeva, Nadejda
collection PubMed
description When viruses like SARS-CoV-2 infect cells, they reprogram the repertoire of cellular and viral transcripts that are being translated to optimize their strategy of replication, often targeting host translation initiation factors, particularly eIF4F complex consisting of eIF4E, eIF4G and eIF4A. A proteomic analysis of SARS-CoV-2/human proteins interaction revealed viral Nsp2 and initiation factor eIF4E2, but a role of Nsp2 in regulating translation is still controversial. HEK293T cells stably expressing Nsp2 were tested for protein synthesis rates of synthetic and endogenous mRNAs known to be translated via cap- or IRES-dependent mechanism under normal and hypoxic conditions. Both cap- and IRES-dependent translation were increased in Nsp2-expressing cells under normal and hypoxic conditions, especially mRNAs that require high levels of eIF4F. This could be exploited by the virus to maintain high translation rates of both viral and cellular proteins, particularly in hypoxic conditions as may arise in SARS-CoV-2 patients with poor lung functioning. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-023-02021-2.
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spelling pubmed-100609392023-03-30 SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions Korneeva, Nadejda Khalil, Md Imtiaz Ghosh, Ishita Fan, Ruping Arnold, Thomas De Benedetti, Arrigo Virol J Research When viruses like SARS-CoV-2 infect cells, they reprogram the repertoire of cellular and viral transcripts that are being translated to optimize their strategy of replication, often targeting host translation initiation factors, particularly eIF4F complex consisting of eIF4E, eIF4G and eIF4A. A proteomic analysis of SARS-CoV-2/human proteins interaction revealed viral Nsp2 and initiation factor eIF4E2, but a role of Nsp2 in regulating translation is still controversial. HEK293T cells stably expressing Nsp2 were tested for protein synthesis rates of synthetic and endogenous mRNAs known to be translated via cap- or IRES-dependent mechanism under normal and hypoxic conditions. Both cap- and IRES-dependent translation were increased in Nsp2-expressing cells under normal and hypoxic conditions, especially mRNAs that require high levels of eIF4F. This could be exploited by the virus to maintain high translation rates of both viral and cellular proteins, particularly in hypoxic conditions as may arise in SARS-CoV-2 patients with poor lung functioning. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-023-02021-2. BioMed Central 2023-03-30 /pmc/articles/PMC10060939/ /pubmed/36998012 http://dx.doi.org/10.1186/s12985-023-02021-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Korneeva, Nadejda
Khalil, Md Imtiaz
Ghosh, Ishita
Fan, Ruping
Arnold, Thomas
De Benedetti, Arrigo
SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions
title SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions
title_full SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions
title_fullStr SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions
title_full_unstemmed SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions
title_short SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions
title_sort sars-cov-2 viral protein nsp2 stimulates translation under normal and hypoxic conditions
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060939/
https://www.ncbi.nlm.nih.gov/pubmed/36998012
http://dx.doi.org/10.1186/s12985-023-02021-2
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