(4d) Viral Peptide Isolated From the Hepatitis C Virus (HCV): Interactions with Lipid Assemblies and Biotechnological Applications

The hepatitis C virus (HCV) is an important cause of worldwide chronic liver disease, infecting over 170 million people. Current treatment for HCV is based on interferon and ribavirin, which are associated with significant toxicities and suboptimal efficacy for many patients, highlighting the need for new therapies. As part of ongoing research to combat HCV, we study how key components of the virus' replication machinery attach to cell membranes.

From our biological studies, we discovered that an amphipathic, α-helical (AH) peptide derived from the HCV NS5A protein can be employed to destabilize vesicles, leading to lipid bilayer formation on gold and titanium oxide substrates. The favorable electrical properties of gold and the biocompatibility of titanium oxide make the formation of model lipid bilayers supported on these substrates attractive platforms for many membrane-associated biological, physiological, and electrochemical applications including biosensors, surface modification of medical implants, and programmed drug delivery devices.

We have determined that the AH peptide-induced structural transformation occurs in a vesicle size-dependent manner. Simultaneous quartz crystal microbalance-dissipation (QCM-D) monitoring and optical reflectometry measurements allowed us to simultaneously follow the acoustic and optical property changes of the vesicle-bilayer structural transformation, and propose a mechanism for the interaction between AH peptides and intact vesicles that provides new insight into the process of vesicle fusion on solid substrates. From this work, we discuss possible applications of lipid bilayers supported on gold and titanium oxide as well as the AH peptide's potential as a novel anti-HCV therapy.