BROADLY REACTIVE ANTIBODIES TO HYPERVARIABLE REGION 1 IN HEPATITIS-C VIRUS-INFECTED PATIENT SERA - RELATION TO VIRAL LOADS AND RESPONSE TO INTERFERON

To clarify the nature of serum anti-hypervariable region 1 (HVR1) anti bodies in patients infected with hepatitis C virus (HCV), we assessed the reactivity of 21 patients' sera with 42 HVR1 proteins by Western b lot. HVR1 was expressed as fusion proteins with glutathione S-transfer ase (GST), The patients' sera reacted with variable percentages of the HVR1 proteins, and always reacted with HVR1 proteins of the different genotype. In the genotype-1b-infected patients, the percentage of gen otype-lb HVR1 proteins reactive with serum correlated significantly wi th viral loads; the sera reactive with the higher percentages of HVR1 proteins contained the larger viral loads. In addition, it was signifi cantly lower in the responders of interferon (IFN) therapy than in non responders. The competition assays indicated that multiple fractions o f anti-HVR1 antibodies with different specificity in a serum reacted w ith different HVR1 proteins, and that, additionally, a single fraction of antibodies often reacted with more than one HVR1 protein through a similar amino acid sequence. In conclusion, serum anti-HVR1 antibodie s were broadly reactive by the mechanism of both the cross-reactivity of a single fraction of anti-HVR1 antibodies with more than one HVR1 p rotein and the presence of multiple fractions of anti-HVR1 antibodies with different specificity in a serum. In genotype-1b-infected patient s, the broad reactivity of serum anti-HVR1 antibodies correlated with viral loads and response to IFN. Further studies are necessary to eluc idate the correlation among the broad reactivity of sera with multiple HVR1 proteins and clinical features of chronic hepatitis C patients.