Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody.
The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density lipoproteins co-fractionated with the low-density particles, and high-density lipoproteins co-fractionated with the intermediate-density particles. Immunoglobulins were found exclusively in the high-density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In antibody-positive, immunocompetent patients, however, virus titres in the low-density fraction and those in the high-density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody-mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high-density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence.
Pumeechockchai
W
W
Centre for Liver Research, Medical School, Newcastle upon Tyne, United Kingdom.
Bevitt
D
D
Agarwal
K
K
Petropoulou
T
T
Langer
B C A
BC
Belohradsky
B
B
Bassendine
M F
MF
Toms
G L
GL
D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics; D016632:Apolipoprotein A-I / Q000276:immunology; D002648:Child; D041321:Chromosomes, Human, X; D017074:Common Variable Immunodeficiency / Q000150:complications; D005260:Female; D040181:Genetic Diseases, X-Linked; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology / Q000821:virology*; D006801:Humans; D007121:Immunocompetence; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011233:Precipitin Tests; D012367:RNA, Viral / Q000097:blood; D014461:Ultracentrifugation; D014771:Virion / Q000276:immunology*
D016632:Apolipoprotein A-I; D018937:Hepatitis C Antibodies; D007136:Immunoglobulins; D012367:RNA, Viral