The most recently discovered herpesvirus, Kaposi’s sarcoma herpesvirus (KSHV/HHV8) is known to cause three human cancers, Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. No cure or vaccine exists for KSHV infection and its associated malignancies. To identify novel KSHV antiviral targets, we propose to identify virus-specific protein functions and protein conformations by employing highly specialized electron microscopy methods to directly visualize purified KSHV DNA replication proteins and viral DNA sequences during the formation of the DNA replication fork at the viral origins of replication.