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

Essential mixed cryoglobulinemia is frequently associated with hepatit is 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 remai ns uncertain whether cryoglobulins (CGs) contain such antibody-bound H CV, Thus, we studied HVR clones isolated from cryoprecipitate and supe rnatant in the sera of four chronic hepatitis C patients with cryoglob ulinemia, and expressed as fusion proteins with glutathione S-transfer ase (GST), Patients' sera were tested for antibody binding to the prot eins, 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 concentrate d in cryoprecipitates compared with those of serum and supernatant in two patients tested. Anti-HVR antibody-positive clones in cryoprecipit ate showed common amino acid (aa) sequences in each of the four patien ts. Similarly, all the antibody-positive clones in supernatant showed the same aa sequences for three of the four patients, When aa sequence s were compared with those of reported isolates with genotype 1b, the mean percentage of aa difference was greater in the clones from supern atant and in anti-HVR antibody-negative clones than in the clones from cryoprecipitate and in the antibody-positive clones, respectively, Th ese findings indicate that serum CG contains anti-HVR antibody-bound H CV in patients with chronic hepatitis C. Anti-HVR antibody-free indivi dual clones, which were more frequently noted in supernatant, showed c losely related sequences, but which were of a heterogeneous quasispeci es nature.