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A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor
The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels (transcript...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773096/ https://www.ncbi.nlm.nih.gov/pubmed/35052693 http://dx.doi.org/10.3390/biomedicines10010013 |
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author | Libre, Camille Seissler, Tanja Guerrero, Santiago Batisse, Julien Verriez, Cédric Stupfler, Benjamin Gilmer, Orian Cabrera-Rodriguez, Romina Weber, Melanie M. Valenzuela-Fernandez, Agustin Cimarelli, Andrea Etienne, Lucie Marquet, Roland Paillart, Jean-Christophe |
author_facet | Libre, Camille Seissler, Tanja Guerrero, Santiago Batisse, Julien Verriez, Cédric Stupfler, Benjamin Gilmer, Orian Cabrera-Rodriguez, Romina Weber, Melanie M. Valenzuela-Fernandez, Agustin Cimarelli, Andrea Etienne, Lucie Marquet, Roland Paillart, Jean-Christophe |
author_sort | Libre, Camille |
collection | PubMed |
description | The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels (transcription, translation, and protein degradation) that altogether reduce the levels of A3G in cells and prevent its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) located within two critical stem-loop structures of the 5′ untranslated region (5′-UTR) of A3G mRNA for this process. A3G translation occurs through a combination of leaky scanning and translation re-initiation and the presence of an intact uORF decreases the extent of global A3G translation under normal conditions. Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules. Overall, we discovered that A3G translation is regulated by a small uORF conserved in the human population and that Vif uses this specific feature to repress its translation. |
format | Online Article Text |
id | pubmed-8773096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87730962022-01-21 A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor Libre, Camille Seissler, Tanja Guerrero, Santiago Batisse, Julien Verriez, Cédric Stupfler, Benjamin Gilmer, Orian Cabrera-Rodriguez, Romina Weber, Melanie M. Valenzuela-Fernandez, Agustin Cimarelli, Andrea Etienne, Lucie Marquet, Roland Paillart, Jean-Christophe Biomedicines Article The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels (transcription, translation, and protein degradation) that altogether reduce the levels of A3G in cells and prevent its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) located within two critical stem-loop structures of the 5′ untranslated region (5′-UTR) of A3G mRNA for this process. A3G translation occurs through a combination of leaky scanning and translation re-initiation and the presence of an intact uORF decreases the extent of global A3G translation under normal conditions. Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules. Overall, we discovered that A3G translation is regulated by a small uORF conserved in the human population and that Vif uses this specific feature to repress its translation. MDPI 2021-12-22 /pmc/articles/PMC8773096/ /pubmed/35052693 http://dx.doi.org/10.3390/biomedicines10010013 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Libre, Camille Seissler, Tanja Guerrero, Santiago Batisse, Julien Verriez, Cédric Stupfler, Benjamin Gilmer, Orian Cabrera-Rodriguez, Romina Weber, Melanie M. Valenzuela-Fernandez, Agustin Cimarelli, Andrea Etienne, Lucie Marquet, Roland Paillart, Jean-Christophe A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor |
title | A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor |
title_full | A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor |
title_fullStr | A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor |
title_full_unstemmed | A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor |
title_short | A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor |
title_sort | conserved uorf regulates apobec3g translation and is targeted by hiv-1 vif protein to repress the antiviral factor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773096/ https://www.ncbi.nlm.nih.gov/pubmed/35052693 http://dx.doi.org/10.3390/biomedicines10010013 |
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