Title |
Regulation of the KSHV Latent Promoter
|
Institution |
UNIV OF NORTH CAROLINA CHAPEL HILL, CHAPEL HILL, NC
|
Principal Investigator |
DITTMER, DIRK
|
NCI Program Director |
Read_Connole
|
Cancer Activity |
Cancer Etiology
|
Division |
DCB
|
Funded Amount |
$227,369
|
Project Dates |
08/01/2004 - 04/30/2015
|
Fiscal Year |
2014
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
Herpes - Other (100.0%)
|
Kaposi Sarcoma (75.0%)
Non Hodgkins Lymphoma (25.0%)
Sarcoma (75.0%)
|
Research Type |
Cancer Initiation: Oncogenes and Tumor Suppressor Genes
Exogenous Factors in the Origin and Cause of Cancer
|
Abstract |
DESCRIPTION (provided by applicant): This is the renewal application for RO1 CA109232 Regulation of the KSHV LANA promoter. It responds to PA PA-07-455 Research on Malignancies in the Context of HIV/AIDS Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is convincingly associated with Kaposi's Sarcoma (KS), an endothelial cell tumor and B-cell lymphoproliferative disease such as PEL in AIDS patients. During latency in KS and B-cell tumors fewer than 5% of KSHV genes are transcribed and these genes are implicated in KSHV episome maintenance and oncogenesis. Our prior real-time QPCR array analysis showed that every KS tumor expressed the viral latent genes and viral microRNAs. In addition a variable fraction also expressed viral lytic genes. Hence the question emerges what regulates KSHV latent genes? Our preliminary data suggest that understanding the latent/lytic switch in KSHV will have a significant impact on KS diagnosis and might uncover novel therapeutic targets to cure latent virus infection. Our new transgenic mouse data demonstrate that this ~1000bp sequence mediated B-cell specific activity of LANAp. We propose to continue our analysis of LANAp, expand the initial grant to in vivo analysis of the B-cell specificity of LANAp, the phenotypic characterization of LANA and KSHV miRNA expression in vivo and the analysis of cellular and viral factors in B cells and appropriate endothelial cell models. nn |