von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step.

Aurélie Mousnier (1) , Nicole Kubat (2) , Aurélie Massias-Simon (1) , Emmanuel Ségéral (2) , Jean-Christophe Rain (3) , Richard Benarous (2) , Stéphane Emiliani (2) , Catherine Dargemont (1)

1 IJM (UMR_7592) - Institut Jacques Monod
2 UMR_S567 / UMR 8104 - Institut Cochin
3 Hybrigenics [Paris]

HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin-proteasome pathway. Here, we identify von Hippel-Lindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel-Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin-VHL-proteasome pathway in the integration-transcription transition of the viral replication cycle.

Domaines: Biochimie [q-bio.BM]

Aurélie Mousnier, Nicole Kubat, Aurélie Massias-Simon, Emmanuel Ségéral, Jean-Christophe Rain, et al.. von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step.. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (34), pp.13615-20. ⟨10.1073/pnas.0705162104⟩. ⟨hal-00182604⟩