Retrovirology (Mar 2012)

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

  • 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,
  • Cusick Michael E,
  • Burny Arsène,
  • Van Lint Carine,
  • Hill David E,
  • Tavernier Jan,
  • Kettmann Richard,
  • Vidal Marc,
  • Twizere Jean-Claude

DOI
https://doi.org/10.1186/1742-4690-9-26
Journal volume & issue
Vol. 9, no. 1
p. 26

Abstract

Read online

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.

Keywords