The Vif protein of human immunodeficiency virus type 1 is posttranslationally modified by ubiquitin.
The viral infectivity factor (Vif), one of the six HIV-1 auxiliary genes, is absolutely necessary for productive infection in primary CD4-positive T lymphocytes and macrophages. Vif overcomes the antiviral function of the host factor APOBEC3G. To better understand this mechanism, it is of interest to characterize cellular proteins that interact with Vif and may regulate its function. Here, we show that Vif binds to hNedd4 and AIP4, two HECT E3 ubiquitin ligases. WW domains present in those HECT enzymes contribute to the binding of Vif. Moreover, the region of Vif, which includes amino acids 20-128 and interacts with the hNedd4 WW domains, does not contain proline-rich stretches. Lastly, we show that Vif undergoes post-translational modifications by addition of ubiquitin both in cells overexpressing Vif and in cells expressing HIV-1 provirus. Vif is mainly mono-ubiquitinated, a modification known to address the Gag precursor to the virus budding site.
Dussart
Sylvie
S
Inserm Unit 372, Université de la Méditerranée, 163 Avenue de Luminy, BP178, 13276 Marseille Cedex 09, France.
Courcoul
Marianne
M
Bessou
Gilles
G
Douaisi
Marc
M
Duverger
Yohann
Y
Vigne
Robert
R
Decroly
Etienne
E
D015153:Blotting, Western; D002460:Cell Line; D056827:Endosomal Sorting Complexes Required for Transport; D015870:Gene Expression; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D000075702:Nedd4 Ubiquitin Protein Ligases; D011233:Precipitin Tests; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus
D056827:Endosomal Sorting Complexes Required for Transport; D016346:Gene Products, vif; D011994:Recombinant Proteins; D012097:Repressor Proteins; D025801:Ubiquitin; D054320:vif Gene Products, Human Immunodeficiency Virus; C432966:ITCH protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase