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

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.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.Human T-cell lymphotropic viruses HTLV-1 and -2 are members of Deltaretrovirus genus of the Retroviridae family [1]. HTLV-1 induces Adult T-cell Leukemia/Lymphoma (ATLL) [2], an aggressive lymphoproliferative disease. HTLV-1 is also associated with tropical spastic paraparesis (TSP) [3], a neurological degenerative syndrome. HTLV-2 is closely related to HTLV-1 but causes no known overt disease [4,5]. The elaborate pathogenicity of HTLV-1 involves establishment and reactivation of latent stages, transcriptional activation of specific cellular genes, and modulation of cell death and proliferation pathways [6]. Modulations of viral and cellular function upon infection rely on crosstalk between the few viral encoded proteins and specific human proteins.HTLV genomes encode structural proteins that form the viral core particle (Gag and Env), and enzymatic retroviral proteins (reverse transcriptase, integrase and protease). HTLV contain a