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.

R01CA079398

1998-09-01

2003-06-30