The contribution of Kaposi Sarcoma Herpesvirus K15 protein to virus-induced pathological angiogenesis

• Applicant: Professor Dr. Thomas Schulz
• Subject Area: Virology
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243563181

Kaposi Sarcoma Herpesvirus (KSHV), also known as Human Herpesvirus 8 (HHV8) is a human gammaherpesvirus and the cause of Kaposi Sarcoma (KS), primary effusion lymphoma (PEL) and most cases of the plasma cell variant of multicentric Castleman Disease (MCD). Kaposi Sarcoma is a poly-/oligoclonal vascular tumour and thought to be derived from lymphatic endothelial cells. Its histology is characterized by latently KSHV-infected atypical endothelial cells, in particular the characteristic spindle cells, as well as signs of a leaky vasculature, atypical endothelial cells exhibiting signs of endothelial-mesenchymal transition (EndMT) and pronounced inflammatory responses. Several viral proteins have been linked to these different histological abnormalities. We have recently shown that the KSHV K15 protein, a distant functional and positional homologue of the Epstein-Barr Virus (EBV) transforming proteins LMP1 and LMP2A, may play a role in KSHV-induced angiogenesis. The aim of this project proposal therefore is to further elucidate the molecular mechanisms by which the K15 protein may alter angiogenesis in order to better understand its contribution to KS pathogenesis. We also want to pursue preliminary results that indicate the possibility of targeting K15-induced signaling cascades in order to block its angiogenic properties.

• DFG Programme: Research Grants