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Published on: July 16, 2012
Sequence analysis of hypervariable region of hepatitis C virus (HCV) associated with immune complex in patients with
T Aiyama1, K Yoshioka, A Okumura
1Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Insights
Hepatitis C virus (HCV) often forms immune complexes (ICs) in patients. These HCV-containing ICs are primarily found in the bottom serum fraction, suggesting antibody responses drive their formation.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Immune complexes (ICs) are common in hepatitis C virus (HCV) infected patients.
- HCV particles in serum can exist as ICs, particularly in the bottom fraction after ultracentrifugation.
Purpose of the Study:
- To investigate the association between circulating immune complexes and HCV RNA distribution in serum.
- To explore the role of antibody response to the hypervariable region (HVR) in HCV-IC formation.
Main Methods:
- Serum fractionation using differential flotation ultracentrifugation.
- Detection of HCV RNA in top and bottom serum fractions.
- Analysis of amino acid sequences in the HCV hypervariable region (HVR) from different fractions.
Main Results:
- HCV RNA was predominantly detected in the bottom fraction (indicating ICs) of IC-positive patients.
- HCV HVR sequences in the bottom fraction closely matched whole serum sequences.
- HCV HVR sequences in the top fraction often differed significantly from whole serum sequences.
Conclusions:
- The majority of circulating HCV in IC-positive patients forms immune complexes.
- Antibody responses targeting the HCV hypervariable region (HVR) are likely responsible for initiating IC formation.
Abstract:
Immune complex (IC) frequently exists in sera of patients with hepatitis C virus (HCV) infection. When circulating HCV particles are fractionated by differential flotation ultracentrifugation, HCV in the bottom fraction appears to be in the form of IC. Flotation ultracentrifugation of serum was done in 7 patients positive for serum anti-C3d-binding circulating IC and in 7 negative patients. In all IC-positive patients, HCV RNA was detected in the bottom fraction but not in the top fraction of 3 patients. Amino acid sequences of hypervariable region (HVR) of HCV in the bottom fraction of IC-positive patients were almost the same as those of whole serum, while those of the top fraction considerably differed from those of whole serum except for 1 case. These data suggest that the major population of HCV forms IC in IC-positive patients, and antibody response to the HVR of HCV is responsible for IC formation.
