Kaposi's sarcoma associate herpesvirus (KSHV) is a tumorigenic gammaherpesvirus associated with AIDS-related malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Herpesviruses exist in two states, a quiescent state of latency and a lytic virus-producing state characterized by expression from the entire viral genome. Reactivation of KSHV from latency results in the expression of lytic genes that potentially contribute to transformation and disease progression (e.g. viral cytokines). Therefore, understanding the mechanism controlling KSHV reactivation is an important public health issue. A KSHV transcriptional activator, Rta, is sufficient and necessary for driving viral reactivation from latency and activating lytic gene expression. The goal of this research proposal is to elucidate the direct viral targets and the cellular targets of Rta. A novel protein delivery method using an HIV-1 Tat peptide fused to Rta will be combined with DNA microarray analysis. Tat-Rta will be exogenously delivered to latently-infected cells in the presence of a protein synthesis inhibitor and gene expression will be screened to determine the direct targets of Rta. Analyzing the viral and cellular gene expression patterns induced by KSHV Rta will provide insight into the molecular interactions regulating the life cycle and pathogenesis of KSHV, and may aid in the development of novel therapeutic regimes for KSHV-associated malignancies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA088517-01
Application #
6209167
Study Section
Special Emphasis Panel (ZRG1-AARR-4 (01))
Program Officer
Lohrey, Nancy
Project Start
2000-09-01
Project End
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$37,516
Indirect Cost
Name
University of California Los Angeles
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Symensma, Tonia L; Martinez-Guzman, DeeAnn; Jia, Qingmei et al. (2003) COX-2 induction during murine gammaherpesvirus 68 infection leads to enhancement of viral gene expression. J Virol 77:12753-63