Communication interception of human signal transduction pathways by Human Immunodeficiency Virus-1

摘要

Signal transduction pathways are central to most biological processes. Diversion of such pathways is postulated to be central to the mechanism by which the Human Immunodeficiency Virus-1 (HIV) takes over the human cellular machinery. In this paper, we present an analysis of the interactions between HIV and human signal transduction pathways. We find that the majority of known human pathways are targeted through at least one HIV, human protein interaction (277 of the 453 pathways we considered). There are some pathways in which HIV interacts with disproportionately many proteins, targeting a single pathway at multiple positions. These numerous interactions are not just a function of the size of the pathways; other large pathways are not necessarily targeted to the same extent. Based on this analysis, we propose a novel rational drug design strategy as one of identifying possible ldquoalternaterdquo pathways. Activating or suppressing them may bypass HIV targeted pathways, thus exploiting redundancies in the human protein interaction network.