APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles.
APOBEC3G is a cytidine deaminase that limits the replication of many retroviruses. This antiviral host factor is packaged into retrovirus particles, where it targets single-stranded DNA generated during reverse transcription and induces up to 2% of G-to-A mutations, which are lethal for the HIV-1 provirus. Vif protein counteracts this antiviral factor by decreasing its packaging into lentivirus particles. Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin ligase, interacts with APOBEC3G, through its WW2 and WW3 domains. As a result of this interaction, APOBEC3G undergoes post-translational modification by addition of ubiquitin moieties. Accordingly, we demonstrate that the dominant negative Nedd4-1 C/S form prevents APOBEC3G ubiquitination. Moreover, the packaging of APOBEC3G into Pr55 Gag virus-like particles and into HIV-1 virions is reduced when Nedd4-1 C/S is expressed. During HIV-1 viral production in the presence of APOBEC3G, Nedd4-1 C/S restores partially the infectivity of Deltavif HIV-1. We conclude that the ubiquitination of APOBEC3G by Nedd4-1 favors its targeting to the virus assembly site where APOBEC3G interacts with Gag and is packaged into HIV-1 particles in the absence of Vif.
Dussart
Sylvie
S
Inserm Unité 372, Université de la Méditerranée, 163 Avenue de Luminy, BP178, 13276 Marseille Cedex 09, France.
Douaisi
Marc
M
Courcoul
Marianne
M
Bessou
Gilles
G
Vigne
Robert
R
Decroly
Etienne
E
D000071480:APOBEC-3G Deaminase; D002352:Carrier Proteins / Q000378:metabolism*; D003564:Cytidine Deaminase; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D009700:Nucleoside Deaminases; D011506:Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D025801:Ubiquitin / Q000378:metabolism*; D019065:Virus Assembly
D002352:Carrier Proteins; D008565:Membrane Proteins; C451223:NDFIP1 protein, human; D011506:Proteins; D012097:Repressor Proteins; D025801:Ubiquitin; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase