The Kaposi's sarcoma-associated herpesvirus (KSHV) is implicated as a causative agent in skin malignancies and some lymphomas. Dr. Medveczky and his colleagues are studying KSHV and a related monkey tumor virus, Herpesvirus saimiri (HVS). KSHV and HVS share genes that are suspected to have roles in immortalization.
The first goal of Dr. Medveczky's current research is to identify essential genetic elements and genes of KSHV and HVS required for latent episomal replication of the viral genome in tumor cells. They identified a viral protein, latency-associated nuclear antigen (LANA), that is required for this process. LANA is a specific DNA-binding protein and interacts with the terminal repeats of the KSHV and HVS genomes. LANA and the repeats are essential and sufficient for maintenance of the viral genome in tumor cells.
The second focus of Dr. Medveczky's studies on HVS is a specific viral gene (TIP) that is essential for malignant transformation. TIP binds and activates a T cell-specific protein kinase, Lck. Activation of Lck leads to induction of STAT transcription factors and activation of downstream genes. Dr. Medvecsky and his colleagues showed that activation of STATs by Lck occurs in the absence of Jak kinases. This area of investigation is important because STATs are induced in human lymphomas and in many other cancers. Therefore, the HVS model provides a unique opportunity to study the roles of Lck and STATs in oncogenic transformation. This system also could be used as an animal model to evaluate drugs designed against Lck and STATs.
Third, Dr. Medveczky's laboratory described that THC, the active compound in marijuana blocks reactivation and replication of oncogenic herpesviruses. Experiments are under way to thest the hypothesis that endogenous cannabinoids may regulate viral latency and reactivation.