Viral manipulation of mitotic and antiviral signal transduction is a fundamental determinant of the outcome of many infections. Crucial, but often poorly understood, protein kinases in these signaling cascades modulate genome-associating proteins in both the cytoplasm and nucleus to direct cell division and host defenses intercepting foreign nucleic acid. Investigating how viruses redirect dynamic phosphorylation of cellular factors addresses key knowledge gaps and uncovers the underlying molecular mechanisms involved. Specifically, the long term goal of our research is to determine how poxviruses usurp and repurpose signaling cascades governing mitotic and host defense effectors. To achieve this goal, our laboratory studies a family of protein kinases comprised of homologs widely expressed in poxviruses and in all multicellular eukaryotes. Growing evidence demonstrates that the homology shared between these viral and cellular kinases allows them to overlap functionally, providing fascinating insights into virus-host interaction at the level of post-translational modification. In this seminar I will present new evidence of how poxviral factors integrate with cellular pathways, revealing how kinases and phosphatases regulate proteins associated with cellular and viral genomes in infected cells.