Summary auto-generated
This study demonstrates a novel in vitro model using primary biliary cells to detect neutralizing antibodies against hepatitis C virus (HCV). The researchers infected human biliary cells with HCV and confirmed infection through RT-PCR detection of HCV RNA and immunohistochemical staining for HCV core protein. They then tested serum samples from ten patients who had achieved long-term sustained response to interferon or interferon-ribavirin therapy. Using this biliary cell infection model, neutralizing antibodies were detected in patient sera at dilutions up to 1:25, and this neutralizing activity was confirmed to be antibody-mediated by testing purified IgG. Notably, neutralizing antibodies were identified after therapy completion but not before treatment initiation. The model successfully detected antibodies capable of neutralizing HCV 1b reference strain even from patients infected with different HCV genotypes, suggesting cross-reactive neutralizing responses. Most sera with neutralizing activity showed serological reactivity to envelope proteins E1 and E2, though one patient displayed neutralizing activity without detectable anti-E1 or anti-E2 antibodies, suggesting conformational epitopes may be important.
Key findings
- Primary biliary cells provide a reproducible in vitro system for detecting HCV infection, confirmed by both PCR and immunohistochemical detection of viral components
- Neutralizing anti-HCV antibodies were detected in sera from patients with sustained virological response to therapy, appearing after treatment completion but not before therapy
- Neutralizing activity persisted long-term in recovered patients (up to 84 months post-therapy) and could be attributed to IgG antibodies through purified immunoglobulin testing
- Sera from patients infected with different HCV genotypes could neutralize HCV 1b reference strain, demonstrating cross-genotypic neutralizing antibody responses
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Abstract
The identification and characterization of neutralizing anti-hepatitis C virus (HCV) antibodies may have a major impact on understanding HCV pathogenesis. However, to date, their detection has only been based on the inhibition of either the E2 envelope protein or HCV virions binding to different target cells. The permissivity of primary biliary cells for HCV infection has been demonstrated previously. In the present report, infection of biliary cells was demonstrated further by combining PCR and immunohistochemical detection of the HCV core protein. This study demonstrates, using both serum and purified IgG, the presence of neutralizing anti-HCV antibodies in the serum of patients showing long-term response to antiviral therapy. Overall, the usefulness of the primary biliary cell infection model to investigate anti-HCV neutralization is shown.