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Antigenic variation of core, NS3, and NS5 proteins among genotypes of hepatitis C virus
J A Neville1, L E Prescott, V Bhattacherjee
1Department of Medical Microbiology, University of Edinburgh, United Kingdom.
Insights
Hepatitis C virus (HCV) antibody screening assays using type 1 antigens may miss infections from other HCV genotypes. This study shows significant type-specific antibody responses, indicating current assays are suboptimal for diverse global populations.
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Hepatitis C virus (HCV) antibody detection is crucial for screening blood donors and diagnosing hepatitis.
- Current enzyme-linked immunosorbent assays (ELISAs) primarily use antigens from HCV type 1.
- HCV exhibits significant genetic variability, with multiple genotypes complicating universal detection.
Purpose of the Study:
- To evaluate the effectiveness of current third-generation ELISA screening assays against diverse HCV genotypes.
- To measure antibody reactivity to genotype-specific and cross-reactive epitopes in patients infected with HCV types 1b, 3a, and 4a.
- To determine the type-specific component of antibody responses to HCV antigens.
Main Methods:
- Sera from 110 hepatitis C patients (genotypes 1b, 3a, 4a) were tested against recombinant proteins from HCV genotypes 1b, 3a, and 4a.
- Recombinant proteins included core, NS3, and NS5 antigens, mirroring those in third-generation ELISAs.
- Serological reactivity to type-homologous and type-heterologous antigens was compared to quantify type-specific responses.
Main Results:
- A significant type-specific antibody response was detected for NS3 (61-77%) and NS5 (60%) antigens.
- Approximately 25% of antibody reactivity to core antigens was type-specific, even between closely related types 1b and 4a.
- These findings align with previous observations of weaker reactivity in assays for non-type 1 infected individuals.
Conclusions:
- Current third-generation HCV antibody screening assays, based on type 1 antigens, are suboptimal for detecting infections across various genotypes.
- The significant type-specific antibody responses highlight the need for more broadly reactive antigens in diagnostic assays.
- Developing assays that accommodate HCV genetic diversity is essential for effective global screening and control strategies.
Abstract:
Assays that detect antibody to hepatitis C virus (HCV) are used to screen blood donors and patients with hepatitis. Current enzyme-linked immunosorbent assay (ELISA)-based methods are invariably based upon antigens from expressed recombinant proteins or oligopeptides from HCV type 1. Some HCV antigens used in screening assays are coded by regions of the HCV genome that show extensive variability; therefore, HCV type 1-based assays may be less effective for the detection of antibody elicited by infection with other genotypes. In this study, we have measured antibody reactivity of sera from 110 hepatitis C patients infected with type 1b, 3a, or 4a to genotype-specific and cross-reactive epitopes present in recombinant proteins from HCV genotypes 1b (core, NS3, and NS5), 3a (NS3, NS5), and 4a (core, NS3), corresponding to those used in current third-generation screening ELISAs. By comparing the serological reactivities of sera to type-homologous and type-heterologous antigens, we detected a significant type-specific component to the reactivity to NS3 (61 to 77% of the total reactivity) and NS5 (60% of the total reactivity). Furthermore, despite the similarities in the amino acid sequences of the core antigens of type 1b and type 4a, we also found significantly greater reactivity to type-homologous antigens, with approximately 25% of reactivity being type specific. These findings are consistent with previous findings of fivefold weaker reactivity of sera from HCV type 2- and HCV type 3-infected blood donors in the currently used third-generation ELISAs and suggest that these assays are suboptimal for screening populations in which the predominant genotype is not type 1.