Human herpesvirus-8 (HHV-8 or KSHV) has been linked to KS and body cavity-based lymphomas. The investigator's laboratory showed that a 60 amino acid kaposin protein encoded by a viral mRNA is expressed in all stages of infection. Kaposin can transform Rat-3 cells in vitro, and the transformed cells caused tumors in nude mice. Therefore, kaposin may play a key role in transformation, and further study of kaposin is important.
Four specific aims are proposed. The first is to determine the transforming domains by generating mutant kaposins. The second is to generate kaposin specific monoclonal antibodies to study the expression of kaposin protein in KS and tumor cells.
The third aim i s to determine the effects of kaposin expression by itself or in combination with other KSHV transforming genes on various endothelial cells and lymphoid cells. The last aim is to determine the mechanism of transformation by focusing on its interaction with growth factor receptors and as a target for phosphorylation by calmodulin-dependent kinase. This study should provide new information on the pathogenesis of HHV-8.
| Muralidhar, S; Veytsmann, G; Chandran, B et al. (2000) Characterization of the human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) oncogene, kaposin (ORF K12). J Clin Virol 16:203-13 |
