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Published on: June 9, 2022
Genetic variability in hepatitis C virus and its role in antiviral treatment response
M Torres-Puente1, J M Cuevas, N Jiménez-Hernández
1Departamento de Genética, Universidad de Valencia, Valencia, Spain.
Insights
Hepatitis C virus (HCV) genetic variability influences treatment response. Higher viral genetic diversity was observed in non-responders compared to responders to alpha interferon and ribavirin therapy.
Area of Science:
- Virology
- Genetics
- Hepatology
Background:
- Hepatitis C virus (HCV) affects 170 million globally, with genetic variability contributing to chronic infection.
- Understanding HCV genetic diversity is crucial for predicting treatment outcomes.
- Combined therapy with alpha interferon and ribavirin is a standard treatment approach.
Purpose of the Study:
- To analyze the genetic variability of HCV in patients before combined antiviral therapy.
- To investigate the correlation between HCV genetic diversity and treatment response (responder vs. non-responder).
- To identify specific genetic markers associated with treatment outcomes.
Main Methods:
- Large-scale sequence analysis of HCV genotype 1 (subtypes 1a and 1b) from 67 patients.
- Analysis of two specific HCV genome regions: hypervariable regions (HVR1-3) of E2 glycoprotein and interferon-sensitive determining region (ISDR)/V3 domain of NS5A protein.
- Comparison of genetic diversity measures and amino acid composition between responder and non-responder groups.
Main Results:
- Higher genetic variability was observed in non-responder patients compared to responder patients.
- Amino acid composition revealed subtype-specific variants but no single position discriminated between responders and non-responders.
- Most amino acid positions were highly conserved, particularly in subtype 1a.
Conclusions:
- HCV treatment outcome likely depends on the combined effect of multiple genetic positions, not just one or two.
- Host immune response plays a significant role in treatment success, alongside antiviral therapy.
- Further research into complex genetic interactions and host factors is warranted for optimizing HCV treatment.
Abstract:
Hepatitis C virus (HCV) is a major health problem worldwide, infecting an estimated 170 million people. The high genetic variability of HCV contributes to the chronicity of hepatitis C. Here, we report results from a large-scale sequence analysis of 67 patients infected with HCV genotype 1, 23 with subtype 1a and 44 with subtype 1b. Two regions of the HCV genome were analysed in samples prior to combined therapy with alpha interferon plus ribavirin, one compressing the hypervariable regions (HVR1, HVR2 and HVR3) of the E2 glycoprotein and another one including the interferon-sensitive determining region (ISDR) and the V3 domain of the NS5A protein. Genetic diversity measures showed a clear tendency to higher genetic variability levels in nonresponder patients to antiviral treatment than in responder patients, although highly disperse values were present within each response group for both subtypes. A more detailed analysis of amino acid composition revealed the presence of several subtype-specific variants in a few positions, but no discriminating positions between responder and nonresponder patients were detected. Our results also revealed that most amino acid positions were highly conserved, especially for subtype 1a. We conclude that the outcome of the antiviral treatment might depend not only on the nature of one or a few independent positions, but more likely on the combination of several positions along the HCV genome. Moreover, the own host's ability to generate an appropriate systemic response, in combination with the action of antivirals, is also likely to be essential for treatment outcome.
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