title: Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses.
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.
authors.affiliation: Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, 450 Brookline Ave,, Boston, MA 02215, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simonis
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rual
authors.forename: Irma
authors.initials: I
authors.lastname: Lemmens
authors.forename: Mathieu
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authors.lastname: Boxus
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirozane-Kishikawa
authors.forename: Jean-Stéphane
authors.initials: JS
authors.lastname: Gatot
authors.forename: Amélie
authors.initials: A
authors.lastname: Dricot
authors.forename: Tong
authors.initials: T
authors.lastname: Hao
authors.forename: Didier
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authors.lastname: Vertommen
authors.forename: Sébastien
authors.initials: S
authors.lastname: Legros
authors.forename: Sarah
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authors.lastname: Daakour
authors.forename: Niels
authors.initials: N
authors.lastname: Klitgord
authors.forename: Maud
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authors.lastname: Martin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Willaert
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authors.lastname: Dequiedt
authors.forename: Vincent
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authors.lastname: Navratil
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: Arsène
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authors.lastname: Burny
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.forename: Richard
authors.initials: R
authors.lastname: Kettmann
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Twizere
mesh_terms: D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity*; D015367:Human T-lymphotropic virus 2 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D049490:Systems Biology / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D020798:Two-Hybrid System Techniques