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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-08, Vol.104 (34), p.13615-13620
• Main Authors: Mousnier, Aurélie, Kubat, Nicole, Massias-Simon, Aurélie, Ségéral, Emmanuel, Rain, Jean-Christophe, Benarous, Richard, Emiliani, Stéphane, Dargemont, Catherine
• Format: Article
• Language: English
• Subjects: Antibodies; Biochemistry; Biochemistry, Molecular Biology; Biological Sciences; Carrier Proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; DNA; Enzymes; Gene expression; Gene Expression Regulation, Viral; Genomes; HeLa Cells; HIV; HIV 1; HIV Integrase; HIV Integrase - genetics; HIV Integrase - metabolism; HIV-1 - genetics; HIV-1 - metabolism; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Infections; Life Sciences; Molecular Chaperones; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Proteasome Endopeptidase Complex; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Proteins; Small interfering RNA; Transcription, Genetic; Transcription, Genetic - genetics; Ubiquitin-Protein Ligases; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitins; Viral DNA; Virus Internalization; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0705162104

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.