Abstract
The eukaryotic genome is organized into distinct structural units dictated by architectural proteins. The major host architectural protein CCCTC-binding factor (CTCF) is usurped by DNA viruses to regulate viral gene expression. This review will discuss the major ways large (EBV, HSV, HCMV) and small (HPV, HBV, AAV) DNA viruses mimic eukaryotic genome topology using CTCF to regulate viral gene expression. We will further discuss how changes in genome topology can drive virally induced oncogenic progression. Knowledge gained from studying viral genome folding mechanisms will inform the development of targeted anti-viral agents and inform the modification of viruses to serve as gene therapy vectors.