Disruption of transcription networks serves as the basis for many diseases. This effect is exemplified by the fact that a variety of viral proteins with oncogenic properties participate in different aspects of viral replication and persistence by disrupting host cell transcription. The viral proteins, Tax and HBZ, fall into this category. These proteins are expressed by the complex retrovirus, Human T-cell Leukemia Virus type 1 (HTLV-1), which is the etiologic agent of a fatal malignancy known as Adult T-cell Leukemia (ATL) as well as a number of immuno-inflammatory diseases. Both Tax and HBZ localize to the nucleus and interact with a wide array of cellular transcriptional regulatory proteins to control viral transcription and alter cellular gene expression. Although these effects are essential for HTLV-1 replication and long-term persistence, they also contribute to the development of ATL and other pathological effects caused by the infection. Our research primarily encompasses three focus points. First, we are interested in identifying which cellular genes are transcriptionally deregulated by Tax and HBZ. Second, we are interested in characterizing how these viral proteins alter transcription of their target genes. Third, we are interested in determining whether these alterations in gene expression are involved in the pathogenic events that may arise during the course of infection, such as T-cell transformation, or whether they facilitate other processes associated with infection, such as viral spread and persistence. This information is requisite to the long-term goal of developing a targeted therapeutic approach to treat ATL patients as well as patients with HTLV-1-mediated inflammatory diseases.