Interaction of a C-terminal Truncated Hepatitis C Virus Core Protein with Plasmid DNA Vaccine Leads to in vitro Assembly of Heterogeneous Virus-like Particles

Recently, it has been shown that HCV core proteins (HCcAg) with C-terminal deletions assemble in vitro into virus-like particles (VLPs) in the presence of structured RNA molecules. Results presented in this work showed that a truncated HCcAg variant covering the first 120 aa (HCcAg. 120) with a 32 aa N-terminal fusion peptide (6xHistag-Xpress (TM) epitope) interacts with plasmid DNA vaccine. Interestingly, the buoyant density of VLPs containing HCcAg. 120 in CsCl gradients changed from 1.15-1,17 g mL(-1) to 1.30-1.34 g mL(-1) after addition of plasmid DNA to assembly reactions. In addition, a delay in electrophoretic mobility of HCcAg. 120-plasmid samples on agarose gels was observed indicating a direct interaction between VLPs and nucleic acids. Remarkably, addition of either plasmid DNA or tRNA to assembly reactions leaded to heterogeneous and larger VLPs formation than those observed in HCcAg. 120 assembly reactions. VLPs containing HCcAg. 120 induced a specific IgG antibodies in mice that reacted with hepatocytes from HCV-infected patients. VLPs obtained in this work would be important to elucidate the mechanisms behind the ability of HCcAg to assemble into a nucleocapsid structure. Besides, the capacity of particles containing HCcAg. 120 to interact with nucleic acids could be used in the development of DNA vaccines and viral vectors based on these particles.