DENSITY ANALYSIS OF HEPATITIS-C VIRUS PARTICLE-POPULATION IN THE CIRCULATION OF INFECTED HOSTS - IMPLICATIONS FOR VIRUS NEUTRALIZATION OR PERSISTENCE

Hepatitis C virus has a low buoyant density in sucrose, but high-densi ty particles are often observed in hepatitis C virus infection. To inv estigate the characteristics of circulating hepatitis C virus particle s and their association with liver disease progression, we examined se ra from two histologically normal hepatitis C virus carriers, 20 chron ic hepatitis patients and five acute hepatitis C patients, The superna tants obtained after immunoprecipitation with anti-immunoglobulins ant ibody were subjected to sucrose equilibrium centrifugation, HCV-RNA po sitive fractions separated after the treatments were further examined for immunoprecipitation with anti-core hepatitis C virus antibody, We separated hepatitis C virus particle populations according to the dens ity difference on 35% sucrose with centrifugation, The proportions of high and low density particles in hepatitis C virus populations were d etermined by means of competitive reverse transcription and polymerase chain reaction. Circulating hepatitis C virus particles in chronicall y infected patients could be separated into two populations: those imm unoglobulin-bound with high densities and -unbound with low densities, Patients with severe liver inflammation had high-density hepatitis C virus that did not precipitate with anti-immunoglobulins but with anti -core hepatitis C virus antibodies, Thus, hepatitis C virus particle p opulations consist of low density virions and high-density immune comp lexes and/or nucleocapsids. Among the chronic hepatitis patients, the dominant population shifted from low-density to high-density particles with the progression of liver disease. In acute hepatitis patients, t his density shift was observed with alanine aminotransferase normaliza tions. Therefore, the major hepatitis C virus populations change from virion to immune complex and/or nucleocapsid with the progression of l iver disease or inflammation.