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-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.
Kanto
T
T
First Department of Medicine, Osaka University Medical School, Japan.
Hayashi
N
N
Takehara
T
T
Hagiwara
H
H
Mita
E
E
Naito
M
M
Kasahara
A
A
Fusamoto
H
H
Kamada
T
T
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*
D000888:Antibodies, Anti-Idiotypic; D007136:Immunoglobulins