Studies outlined in this proposal are designed to investigate the mechanisms that regulate human herpes virus 8 (HHV-8), a virus which is believed to be the causative agent of Kaposi's sarcoma, effusion lymphoma in AIDS patients and multiple myeloma. First, catalytic RNA molecules (ribozymes) that specifically inhibit expressio of HHV-8 genes that are likely to be involved in the pathogenesis of Kaposi's sarcoma will be developed. During design of these anti-HHV-8 ribozymes, steps will be taken to optimize their antiviral effect. Second anti-HHV-8 ribozymes, will be used to inhibit HHV-8 gene expression during latent and lytic viral replication in cultured cells. These experiments will help to determine the role of these HHV-8 genes in the regulation of viral replication. Lastly, the structure and cellular micro-localization of an HHV-8 RNA that is likely to be important in viral pathogenesis will be studied. Although the primary intentio of this work is to study the roles of key HHV-8 genes in viral pathogenesis, i is expected that these studies will also help to identify new therapeutic approaches to the treatment of Kaposi's sarcoma and other HHV-8 related cancer in persons with AIDS.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA079398-03
Application #
6174083
Study Section
AIDS and Related Research Study Section 4 (ARRD)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1998-09-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$222,080
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
White, I E; Campbell, T B (2000) Quantitation of cell-free and cell-associated Kaposi's sarcoma-associated herpesvirus DNA by real-time PCR. J Clin Microbiol 38:1992-5
Campbell, T B; Fitzpatrick, L; MaWhinney, S et al. (1999) Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) infection in men receiving treatment for HIV-1 infection. J Acquir Immune Defic Syndr 22:333-40