Hypervariable region sequence in cryoglobulin-associated hepatitis C virus in sera of patients with chronic hepatitis C: relationship to antibody response against hypervariable region genome

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
T AiyamaS Kakumu

Abstract

Essential mixed cryoglobulinemia is frequently associated with hepatitis C virus (HCV) infection, with the formation of HCV antigen/antibody complexes. The hypervariable region (HVR) of the HCV E2/NS1 region is thought to include epitopes for neutralizing antibodies, but it remains uncertain whether cryoglobulins (CGs) contain such antibody-bound HCV. Thus, we studied HVR clones isolated from cryoprecipitate and supernatant in the sera of four chronic hepatitis C patients with cryoglobulinemia, and expressed as fusion proteins with glutathione S-transferase (GST). Patients' sera were tested for antibody binding to the proteins. The rate of anti-HVR antibody-positive clones was significantly higher in cryoprecipitate (89% +/- 13%, P < .05) than in supernatant (41% +/- 25%). Both HCV RNA and anti-HVR antibody were more concentrated in cryoprecipitates compared with those of serum and supernatant in two patients tested. Anti-HVR antibody-positive clones in cryoprecipitate showed common amino acid (aa) sequences in each of the four patients. Similarly, all the antibody-positive clones in supernatant showed the same aa sequences for three of the four patients. When aa sequences were compared with those of reported isolates with geno...Continue Reading

Citations

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