The entire core protein of HCV JFH1 is required for efficient formation of infectious JFH1 pseudoparticles

The vast majority of hepatitis C virus (HCV) strains cannot be grown in cell culture. Therefore, tests for neutralizing antibodies have relied heavily on retrovirus pseudoparticles displaying the envelope glycoproteins of HCV on their surface (HCVpp). Unfortunately, the envelope proteins of some strains, especially of JFH1, did not efficiently form functional HCVpp. We have manipulated the length and composition of the HCV core gene in the HCVpp expression vectors for three strains of HCV in an attempt to obtain more efficient production of pseudoparticles. The results demonstrated that the truncated core region included in the HCV expression plasmids of the classic pseudoparticle system was optimal for formation of strain H77pp, suboptimal for strain J6pp, and insufficient for strain JFH1pp. Efficiency of JFH1pp formation increased 20-fold when the truncated core gene was replaced with the entire core gene. The full core from J6 and HK had modest effect on the production of infectious J6 and HKpp. The data suggested that pairs of HCV glycoproteins differ inherently in their ability to associate into functional heterodimers and that the core protein, provided in cis as the beginning of the polyprotein product, can in some cases facilitate this process, possibly by increasing the rate of proper folding of the glycoproteins.