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

Autor: 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
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Retrovirology, Vol 9, Iss 1, p 26 (2012)
Druh dokumentu: article
ISSN: 1742-4690
DOI: 10.1186/1742-4690-9-26
Popis: 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.
Databáze: Directory of Open Access Journals