Physical characteristics of the virus

Prior to the discovery of HCV, chimpanzee studies showed that a NANB agent passed through a filter that excluded agents greater than 80 nm in size, suggesting that the responsible pathogen was probably a virus (Bradley et al., 1985; He et al., 1987). In addition, the sensitivity of the pathogen to chloroform indicated that the NANB agent was probably enveloped (Bradley et al., 1983; Feinstone et al., 1983). Molecular cloning and sequencing of the HCV genome further supported these findings (Choo et al., 1989). When virus particles were characterized by banding on sucrose density gradients, infectious sera contained HCV with densities less than 1.06 g/ml while noninfectious sera contained particles banded at approximately 1.12–1.17 g/ml (Miyamoto et al., 1992; Hijikata et al., 1993c). Although both peaks contained detectable HCV RNA, it was subsequently shown that the lighter peak was associated with low density lipoproteins (LDLs) (Miyamoto et al., 1992; Thomssen, Bonk & Thiel, 1993), while the fractions with higher density were associated with immunoglobulins (Hijikata et al., 1993c; Choo et al., 1995). This was verified in experiments showing that the lighter peak was immunoprecipitated with anti-apolipoprotein sera, while the heavier peak was immunoprecipitated with anti-immunoglobulin (Yoshikura et al., 1996). Some of the material in the heavier fractions may also contain nucleocapsids (Kaito et al., 1994; Kanto et al., 1994), which may arise directly from the lysis of hepatocytes supporting virus replication during a bout of liver disease.