GMB A major focus in the laboratory involves investigation of events in the pathogenesis of Kaposi's sarcoma. We are utilizing a multidisciplinary approach with clinical, epidemiological and basic components, involving collaborations with investigators at Emory, the Centers for Disease Control and Prevention and other institutions. Kaposi's sarcoma is a multifocal neoplasm that develops in a high proportion of HIV-infected patients. HHV8 sequences have been found in Kaposi's sarcoma lesions from patients in all known risk groups.
Controversy continues as to the prevalence and cellular distribution of the virus.
Using molecular, cellular, and immunologic techniques, we are determining the prevalence of HHV8 in clinical specimens from various populations, characterizing viral gene expression, and characterizing changes in cellular distribution, viral load, and viral gene expression in various clinical scenarios in Kaposi's sarcoma patients and in patients at risk for Kaposi's sarcoma. We are also characterizing the consequences of expression of several of the HHV8-encoded genes, including vIRF, a interferon regulatory factor homolog that blocks normal cellular responses to interferons. We are exploring themolecular mechanism of its ability to interfere with interferon signaling. The role of PKR in endothelial responses to several RNA viruses, including measles and Ebola, is also under investigation. Human herpesvirus 8 encodes an IRF homologue that represses IRF-1 mediated transcription.