A conserved uORF regulates APOBEC3G translation and is targeted by HIV-1 Vif protein to repress the antiviral factor

Please always quote using this URN: urn:nbn:de:bvb:20-opus-252147
  • 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 conservedThe 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.show moreshow less

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Metadaten
Author: Camille Libre, Tanja Seissler, Santiago Guerrero, Julien Batisse, Cédric Verriez, Benjamin Stupfler, Orian Gilmer, Romina Cabrera-Rodriguez, Melanie M. Weber, Agustin Valenzuela-Fernandez, Andrea Cimarelli, Lucie Etienne, Roland Marquet, Jean-Christophe Paillart
URN:urn:nbn:de:bvb:20-opus-252147
Document Type:Journal article
Faculties:Fakultät für Biologie
Language:English
Parent Title (English):Biomedicines
ISSN:2227-9059
Year of Completion:2021
Volume:10
Issue:1
Article Number:13
Source:Biomedicines (2022) 10:1, 13. https://doi.org/10.3390/biomedicines10010013
DOI:https://doi.org/10.3390/biomedicines10010013
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:APOBEC3G; HIV-1; Vif; mRNA; translation; uORF
Release Date:2023/05/26
Date of first Publication:2021/12/22
EU-Project number / Contract (GA) number:RTI2018-093747-B-10
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International