There is strong evidence that human herpesvirus contribute to the development of Kaposi's sarcoma. Chang and colleagues first identified this virus in autopsy material of a patient with HIV-related Kaposi's sarcoma. Subsequent studies have found this virus to be present in lesions and blood taken from classic, HIV-associated, African, and immunosuppression-associated cases of KS. HHV8 has been implicated in Castleman's disease, and primary effusion lymphomas as well. While the majority of HHV8 infected cells in KS lesions express latent transcripts, replicating virus is present and may contribute to the proliferative process. The P.I. has identified fluctuations in circulating HHV-8 load that correlated with KS progression in a few patients. To date HHV-8 proteins that play a role in the regulation of viral replication has not been identified. One gene with the potential for such a role is the HHV8 ORF50 encoded homologue of the EBV epithelial """"""""lytic switch"""""""" gene BRLFI (R, Rta, R transactivator). The P.I. hypothesize that the transactivation function encoded by ORF50 regulates the expression of HHV8 genes required for viral replication and does so by means of classical transcriptional activation.
The specific aims for this work are: 1. To identify of the complete ORF50 CDNA; 2. To identify HHV8 genes which are responsive to ORF50 mediated activation.; 3 To characterize the mechanism of ORF 50 activation; 4. To identify expression of ORF50 in patients infected with HHV8. Results could be the basis for planning future studies of lytic gene expression, gene regulation and potential novel treatments of KS.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA079334-03
Application #
6173909
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1998-08-01
Project End
2002-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
3
Fiscal Year
2000
Total Cost
$128,135
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599