TY  - JOUR
A1  - Libre, Camille
A1  - Seissler, Tanja
A1  - Guerrero, Santiago
A1  - Batisse, Julien
A1  - Verriez, Cédric
A1  - Stupfler, Benjamin
A1  - Gilmer, Orian
A1  - Cabrera-Rodriguez, Romina
A1  - Weber, Melanie M.
A1  - Valenzuela-Fernandez, Agustin
A1  - Cimarelli, Andrea
A1  - Etienne, Lucie
A1  - Marquet, Roland
A1  - Paillart, Jean-Christophe
T1  - A conserved uORF regulates APOBEC3G translation and is targeted by HIV-1 Vif protein to repress the antiviral factor
JF  - Biomedicines
N2  - 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.
KW  - HIV-1
KW  - APOBEC3G
KW  - Vif
KW  - mRNA
KW  - translation
KW  - uORF
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252147
SN  - 2227-9059
VL  - 10
IS  - 1
ER  -