Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses

Retrovirology

Jean-Claude Twizere⁵  Marc Vidal⁴  Richard Kettmann⁵  Jan Tavernier²  David E Hill⁴  Carine Van Lint⁷  Arsène Burny⁵  Michael E Cusick⁴  Vincent Navratil⁶  Franck Dequiedt⁵  Jean-François Willaert⁵  Maud Martin⁵  Niels Klitgord⁴  Sarah Daakour⁵  Sébastien Legros⁵  Didier Vertommen³  Tong Hao⁴  Amélie Dricot⁴  Jean-Stéphane Gatot⁷  Tomoko Hirozane-Kishikawa⁴  Mathieu Boxus⁵  Irma Lemmens²  Jean-François Rual⁴  Nicolas Simonis¹ 

[1] Laboratoire de Bioinformatique des Génomes et des Réseaux (BiGRe), Université Libre de Bruxelles, Campus Plaine, CP 263, Boulevard du Triomphe, 1050 Bruxelles, Belgium;Department of Medical Protein Research, VIB, Ghent University, B-9000 Ghent, Belgium;Hormones and Metabolism Unit, Université catholique de Louvain and de Duve Institute, 75 Avenue Hippocrate, 1200 Brussels, Belgium;Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA;Protein Signaling and Interactions - GIGA Research Center and Department of Chemistry - Gembloux ABT, University of Liège, 1 avenue de l'Hôpital, 4000 Liege, Belgium;Ecole Nationale Vétérinaire de Lyon, Université de Lyon, INRA, UMR754, and INSERM, U851, 21 avenue Tony Garnier, Lyon F-69007, France;Laboratory of Molecular Virology, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 12 Rue des Profs Jeener et Brachet, 6041 Gosselies, Belgium

关键词: HBZ;    Tax;    ORFeome;    Retrovirus;    Interactome;    HTLV;   

Others  :  1209319
DOI  :  10.1186/1742-4690-9-26

 received in 2011-10-13, accepted in 2012-03-29,  发布年份 2012

【 摘 要 】

Background

Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression.

Results

We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway.

Conclusions

This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection.

【 授权许可】

   
2012 Simonis et al; licensee BioMed Central Ltd.

【 图 表 】

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