Host-Pathogen Interactome Mapping for HTLV-1 and -2 Retroviruses

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Host-Pathogen Interactome Mapping for HTLV-1 and -2 Retroviruses

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Title: Host-Pathogen Interactome Mapping for HTLV-1 and -2 Retroviruses
Author: Simonis, Nicolas; Rual, Jean-François; Lemmens, Irma; Boxus, Mathieu; Hirozane-Kishikawa, Tomoko; Gatot, Jean-Stéphane; Dricot, Amélie; Hao, Tong; Vertommen, Didier; Legros, Sébastien; Daakour, Sarah; Klitgord, Niels; Martin, Maud; Willaert, Jean-François; Dequiedt, Franck; Navratil, Vincent; Burny, Arsène; Van Lint, Carine; Tavernier, Jan; Kettmann, Richard; Twizere, Jean-Claude; Cusick, Michael; Hill, David E.; Vidal, Marc

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Citation: Simonis, Nicolas, Jean-François Rual, Irma Lemmens, Mathieu Boxus, Tomoko Hirozane-Kishikawa, Jean-Stéphane Gatot, Amélie Dricot, et al. 2012. Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses. Retrovirology 9:26.
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Abstract: 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.
Published Version: doi:10.1186/1742-4690-9-26
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