We have continued our studies on delineating the role of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, in the pathogenesis of KS. Over the past year, we have pursued a variety of projects in this area. Firstly, as collaborators, we completed and published studies on two genetic polymorphisms (in the FcgammaRIII gene and IL-6 promoter) that were associated with an increased risk of developing KS. These data point to the importance of the immune response in controlling KSHV-mediated disease. Secondly, we have a paper in press that further details the ultrastructural features of KSHV-infected B cells and endothelial cells. This work builds on our previous studies that examined the morphologic effects of KSHV on infected cells. Most of the work in the past year, however, has focused on identifying molecules and conditions, as well as signal transduction pathways, involved in induction or inhibition of KSHV reactivation. Importantly, this effort has led to three submitted manuscripts: one outlining the effects of corticosteroids on KSHV reactivation, a second that links hypoxic conditions to KSHV reactivation, and a third that describes distinct yet synergistic signal transduction pathways involved in KSHV reactivation. Current studies are focused on defining cell-mediated immune responses directed against KSHV and on creating novel transgenic mouse models for KS. Together, these studies contribute to understanding of how KSHV may cause KS and may aid in the design of novel antiviral and immunotherapeutic treatments for patients with this disease. 100% AIDS-RELATED
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