The tyrosine kinases Fyn and Hck favor the recruitment of tyrosine-phosphorylated APOBEC3G into vif-defective HIV-1 particles.
The main function of Vif is to limit the antiviral activity of APOBEC3G by counteracting its packaging into HIV-1 virions. In this work, we examine the possible functional interactions between Vif, APOBEC3G, and two Src family tyrosine kinases, Fyn and Hck, present in T lymphocytes and in monocyte-macrophages, respectively. By GST pull-down, we show that the SH3 domains of Fyn and Hck, and the corresponding full-length proteins bind Vif of HIV-1. One consequence of this interaction is a reduction in their catalytic activity. Interestingly, we also observed that APOBEC3G can be phosphorylated on tyrosine in the presence of Fyn or Hck, suggesting that both kinases may regulate APOBEC3G function. Accordingly, we demonstrate that in the presence of Fyn or Hck and in the absence of Vif, the overall level of APOBEC3G incorporated into HIV-1 particles is decreased, whereas the level of encapsidation of its phosphorylated form is significantly enhanced.
Douaisi
Marc
M
INSERM Unité 372, Université de la Méditerranée, 163 Avenue de Luminy, BP178, 13276 Marseille Cedex 09, France.
Dussart
Sylvie
S
Courcoul
Marianne
M
Bessou
Gilles
G
Lerner
Edwina C
EC
Decroly
Etienne
E
Vigne
Robert
R
D000071480:APOBEC-3G Deaminase; D001665:Binding Sites; D003564:Cytidine Deaminase; D016346:Gene Products, vif / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D009700:Nucleoside Deaminases; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014443:Tyrosine / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C496631:HCK protein, human; D051076:Proto-Oncogene Proteins c-fyn; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase