Apurva Govande Rose Hills
Proteasomal Inhibition by KSHV Protein ORF68
A virus can have two distinct life cycles: lytic, which produces new virus, and latent, in which the virus remains silently integrated into the DNA of the host. The ultimate goal of a latent virus like Kaposis sarcoma-associated herpesvirus (KSHV) is to get its viral genes integrated into the host genome, and eventually produce viral proteins in order to generate more virus. These viral proteins interact with the host cell organelles and proteins in order to hijack host machinery for viral use. A KSHV viral protein, ORF68, interacts with and inhibits the activity of the host cell proteasome. The proteasome is an ATP dependent, multi-subunit, multi-protein complex that is part of many cellular pathways in the cell, including protein degradation and quality control. Studies have shown that proteasome inhibitors can be used as novel cancer therapies. The proteasome degrades unneeded or misfolded proteins and plays roles in regulating the cell cycle and immune response. My project aims to determine the nature of the interaction between ORF68 and the host proteasome. This interaction will give insight into the role of protein degradation in viral replication and proliferation, eventually leading to novel ways of disrupting the viral life cycle of KSHV.