Research Overview
Angiogenesis and pathogenesis of Kaposi's sarcoma
Kaposi's sarcoma (KS) is a frequent complication of HIV infection among male homosexuals and results in morbidity and mortality for the affected population. KS appears as multifocal tumors that are characterized by intense angiogenesis (neovascularization) and the proliferation of spindle shaped cells. The identities of the malignant cells and etiologic agent of KS remain unclear. The prevalence of KS among HIV-infected homosexuals suggests the involvement of a sexually transmitted agent. Recently, a new member of the herpesvirus family, Human herpesvirus-8 (HHV8-KSHV) has been implicated in KS pathogenesis.
We succeeded in isolating, for the first time, infectious viral particles of HHV-8/KSHV, and we showed that this is a transmissible virus that infects B-cells. Since HHV-8/KSHV is related to oncogenic herpesviruses, and is also associated with certain AIDS B-cell lymphomas, we believe that HHV-8/KSHV infected cells play a central role in KS pathogenesis. We are currently investigating the role of HHV-8/KSHV infection in KS pathogenesis at three levels.
We are using HHV-8/KSHV infected cells and cells transfected with pieces of the HHV-8/KSHV genome or HHV-8/KSHV gene-expression vectors, to investigate how KSHV infection can cause transformation and angiogenesis. We are testing, in cellular and animal models, if KSHV infection and KSHV genes can cause angiogenicity, promote inflammation or induce transformation. Our work showed that KSHV/HHV-8 carries a G-protein coupled receptor oncogene that is able to subvert host protein kinase signaling pathways to cause transformation, and trigger and angiogenic response mediated by VEGF, a major host angiogenic factor and KS cell growth factor.
We believe that understanding how this human oncogenic virus works will help us to better understand cell transformation and the molecular and cellular mechanisms of angiogenesis.
