In this study, we searched for HCV particle in the blood of patients with hepatitis C and found virus-like particles with pleomorphism in size and shape by the electron microscopic observation. First, we attempted to visualize HCV particle by indirect immunogold electron microscopy, using specific antibodies to the HCVE1 protein, and succeeded in identifying HCV virion in HCV-RNA-rich samples. HCV virious, immunologically discriminated from pleomorphic virus-like particles, were 55-65 nm spherical particles with delicate 6 nm-long surface projections. Subsequently, we detected the coincidence of antigenic activities of HCVE2/NS1 and HCVE1 proteins on the surface of HCV particle by the immunogold electron microscopy using anti-HCVE2/NS1 and/or anti-HCVE1 anti-bodies. This result indicates that both HCVE1 and HCVE2/NS1 proteins are components of the envelope of HCV virion, as presumed on the basis of the construct of HCV genome.
Our research also showed that pleomorphic virus-like particles, distinct from HCV,existed in the blood from hepatitis C patients and non-B,non-C hepatitis patients with high incidence. Prevalence of circulating pleomorphic virus-like particles was significantly correlated with the elevation in ALT levels. Although GBV-C-RNA was not detected in any samples containing these virus-like particles and genomic characterization has not been further achieved, it should be done to clarify the nature of these pleomorphic virus-like particles.