Role of the CTCF Binding Site in Human T-Cell Leukemia Virus-1 Pathogenesis

Human T-cell leukemia virus type 1 (HTLV-1) is a cause of leukemia and lymphoma, and several inflammatory medical disorders. The virus integrates in the host cell DNA, and it includes a single binding site for a cellular protein designated CTCF. This protein is important in regulation of many viruses, as well as properties of normal and malignant cells. In order to define the role of CTCF in HTLV-1 pathogenesis in vivo, we analyzed a mutant virus lacking the binding site in humanized mice. We found that this mutation slowed virus spread and attenuated the development of disease. Gene expression studies demonstrated a dynamic role of CTCF in regulating viral gene expression and T lymphocyte activation.