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The Tyrosine Kinase Hck Is an Inhibitor of HIV-1 Replication Counteracted by the Viral Vif Protein

par Hassaïne, Ghérici;Courcoul, Marianne;Bessou, Gilles;Barthalay, Yves;Picard, Christophe;Olive, Daniel;Collette, Yves ;Vigne, Robert;Decroly, Etienne
Référence The Journal of biological chemistry, 276, 20, page (16885-16893)
Publication Publié, 2001-05

Article révisé par les pairs

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Résumé :

The virus infectivity factor (Vif) protein facilitates the replication of human immunodeficiency virus type 1 (HIV-1) in primary lymphocytes and macrophages. Its action is strongly dependent on the cellular environment, and it has been proposed that the Vif protein counteracts cellular activities that would otherwise limit HIV-1 replication. Using a glutathione S-transferase pull-down assay, we identified that Vif binds specifically to the Src homology 3 domain of Hck, a tyrosine kinase from the Src family. The interaction between Vif and the full-length Hck was further assessed by co-precipitation assays in vitro and in human cells. The Vif protein repressed the kinase activity of Hck and was not itself a substrate for Hck phosphorylation. Within one single replication cycle of HIV-1, Hck was able to inhibit the production and the infectivity of vif-deleted virus but not that of wild-type virus. Accordingly, HIV-1 vif- replication was delayed in Jurkat T cell clones stably expressing Hck. Our data demonstrate that Hck controls negatively HIV-1 replication and that this inhibition is suppressed by the expression of Vif. Hck, which is present in monocyte-macrophage cells, represents the first identified cellular inhibitor of HIV-1 replication overcome by Vif.