title: Density analysis of hepatitis C virus particle population in the circulation of infected hosts: implications for virus neutralization or persistence.
abstract: Hepatitis C virus has a low buoyant density in sucrose, but high-density particles are often observed in hepatitis C virus infection. To investigate the characteristics of circulating hepatitis C virus particles and their association with liver disease progression, we examined sera from two histologically normal hepatitis C virus carriers, 20 chronic hepatitis patients and five acute hepatitis C patients. The supernatants obtained after immunoprecipitation with anti-immunoglobulins antibody were subjected to sucrose equilibrium centrifugation. HCV-RNA positive 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 density difference on 35% sucrose with centrifugation. The proportions of high and low density particles in hepatitis C virus populations were determined by means of competitive reverse transcription and polymerase chain reaction. Circulating hepatitis C virus particles in chronically infected patients could be separated into two populations: those immunoglobulin-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 populations consist of low-density virions and high-density immune complexes 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, this density shift was observed with alanine aminotransferase normalizations. Therefore, the major hepatitis C virus populations change from virion to immune complex and/or nucleocapsid with the progression of liver disease or inflammation.
authors.affiliation: First Department of Medicine, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kanto
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Takehara
authors.forename: H
authors.initials: H
authors.lastname: Hagiwara
authors.forename: E
authors.initials: E
authors.lastname: Mita
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: A
authors.initials: A
authors.lastname: Kasahara
authors.forename: H
authors.initials: H
authors.lastname: Fusamoto
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000097:blood* / Q000821:virology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011233:Precipitin Tests; D014771:Virion / Q000302:isolation & purification*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007136:Immunoglobulins