Project 3 Project Summary Abstract Globally, oncogenic DNA viruses cause a significant cancer burden. These viruses establish life-long persistence in the human host and are associated with the development of epithelial, endothelial, and B cell cancers. The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated virus (KSHV) are associated with B cell lymphomas, Kaposi’s sarcoma, gastric cancer, and nasopharyngeal carcinoma (NPC). Moreover, human papillomavirus (HPV) is associated with oropharyngeal and cervical carcinoma. In this application, we propose to explore how the oncogenic gammaherpesviruses, KSHV and EBV, modulate cellular pathways including adenosine-related signaling pathways and how they contribute to oncogenesis. Investigating the various mechanisms involved in modulation of host immunity and oncogenesis by these tumor viruses will inform our understanding of the biology and pathogenesis of these viruses. Our findings will also pave the way for future therapies to treat virus-associated cancers.