Bogenberger, James M., authorLaybourn, Pau, advisor2024-03-132024-03-132008https://hdl.handle.net/10217/237591Human T Lymphotropic Virus Type 1 (HTLV-1) is an oncogenic retrovirus that causes adult T-cell leukemia/lymphoma (ATLL). The virally encoded Tax protein is thought to be necessary and sufficient for T-cell leukemogenesis. Tax promotes cell proliferation, represses multiple DNA repair mechanisms, deregulates cell cycle checkpoints, inhibits apoptosis and induces genomic instability. All of these effects of Tax are thought to cooperate in the development of ATLL. In this study, we demonstrate that histone protein levels are reduced in HTLV-1 infected T-cell lines as compared to uninfected T-cell lines, while the relative amount of DNA per haploid complement is unaffected. In addition, we show that replication-dependent histone transcript levels are reduced in HTLV-1 infected T-cell lines, relative to uninfected T-cell lines. Furthermore, we show that Tax expression is sufficient for reduction of replication-dependent histone transcript levels. These results demonstrate that Tax disrupts the proper regulation of replication-dependent histone gene expression. Further, our findings suggest that HTLV-1 infection uncouples replication-dependent histone gene expression and DNA replication, allowing the depletion of histone proteins with cell division. Histone proteins are involved in the regulation of all metabolic processes involving DNA including transcription, replication, repair and recombination. This study provides a previously unidentified mechanism by which Tax may directly induce chromosomal instability and deregulate gene expression through reduced histone levels.born digitaldoctoral dissertationsengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.molecular biologycellular biologyvirologyHuman T Lymphotropic Virus Type 1 protein Tax reduces histone levelsTextPer the terms of a contractual agreement, all use of this item is limited to the non-commercial use of Colorado State University and its authorized users.