Enhanced-Transient Expression of Hepatitis C Virus Core Protein in Nicotiana tabacum, a Protein With Potential Clinical Applications

Mohammadzadeh, Sara; Khabiri, Alireza; Roohvand, Farzin; Memarnejadian, Arash; Salmanian, Ali Hatef; Ajdary, Soheila; Ehsani, Parastoo

Hepatitis C virus (HCV), the major cause of blood-borne chronic hepatitis with potential progression to cirrhosis, has infected around 170 million people globally (1) . Due to heterogeneity of HCV proteins, their high mutation rates and complex pathogenesis, no approved vaccine for human application against this viral infection is available to date (2, 3) . Recognition of conserved epitopes in HCV proteins and advancements in the formulation of vaccines in novel modalities, however, have led to the placement of a few HCV vaccines in the pipeline of human clinical trials in recent years (4, 5) . HCV holds a single-stranded positive-sense RNA genome which encodes for three structural (core protein and envelope proteins E1 and E2) and six nonstructural proteins (4) . Among the HCV proteins, core (HCVcp) is the most conserved HCV antigen, and hence, a good candidate to be considered for HCV vaccine formulations (4) (5) (6) . Accordingly, application of even isolated HCVcp-CTL epitopes (8-10 amino acids) in the context of synthetic multi-epitope HCV vaccines has also been reported (7) (8) (9) . Besides, anticore antibodies are the first to be raised after the onset of infection, a property that has provided an important diagnostic value for this protein and has located it among antibody-capturing antigens in commercially available serological assays for HCV diagnosis (10) . In addition, nucleotide sequence of HCVcp is supposed to encode for other alternated frame-shift proteins (ARFPs) with important pathogenic roles in chronic HCV infection and cirrhosis (4, 11) . Therefore, to fulfill different diagnostic, research and therapeutic demands, production of HCVcp in various expression systems has been addressed (4) (5) . However, since the C-terminal hydrophobic region of HCVcp exerts immune-suppressive effects (4, 12) , its first 120 N-terminal residues, the hydrophilic region (HCVcp N-120), which contains both nuclear localization signals (NLS) (13) and most of the conserved B and T cell epitopes, is usually employed for different diagnostic (10, 14) and vaccine applications (15) (16) (17) .