Selection of Hepatitis C Virus Resistant to Ribavirin
Author Information
Author(s): Feigelstock Dino A, Mihalik Kathleen B, Feinstone Stephen M
Primary Institution: Division of Viral Products, Center for Biologics Evaluation and Research, FDA
Hypothesis
Understanding HCV resistance to ribavirin could be of major importance for developing interferon-free therapies.
Conclusion
It is possible to select a ribavirin resistant mutant of HCV that can replicate to levels similar to wild type virus grown without ribavirin.
Supporting Evidence
- A concentration of 125 uM of ribavirin did not have a dramatic effect on HCV replication.
- Virus recovered from these cultures were more resistant to 250 uM ribavirin than wild type virus.
- The ribavirin resistant virus accumulated multiple synonymous and non-synonymous mutations.
Takeaway
Researchers found a way to create a version of the hepatitis C virus that can survive even when a medicine called ribavirin is present, which helps us understand how the virus can resist treatment.
Methodology
The J6/JFH1 strain of HCV was serially passed in Huh7D cells in the presence of different concentrations of ribavirin, and virus replication was assessed by detection of HCV antigens and titration of recovered virus.
Limitations
The in vivo relevance of the findings is uncertain, as the ribavirin concentrations used in the study were higher than those typically found in patients.
Digital Object Identifier (DOI)
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