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.
| Seaman, William T; Quinlivan, E Byrd (2003) Lytic switch protein (ORF50) response element in the Kaposi's sarcoma-associated herpesvirus K8 promoter is located within but does not require a palindromic structure. Virology 310:72-84 |
| Seaman, W T; Ye, D; Wang, R X et al. (1999) Gene expression from the ORF50/K8 region of Kaposi's sarcoma-associated herpesvirus. Virology 263:436-49 |
