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A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C
- Source :
-
Journal of Virological Methods . Jun2003, Vol. 110 Issue 2, p201. 9p. - Publication Year :
- 2003
-
Abstract
- Overall treatment results of chronic hepatitis C have improved markedly with the introduction of pegylated interferon-alpha (PEG–IFN-α) and ribavirin combination therapy. However, cure rates in the most common genotype 1 infection are still unsatisfactory. IFN-α dose–response studies on viral kinetics suggest that inadequate dosing might be a key factor but drug levels have hardly been tested, which is in part due to difficulties in measuring this cytokine in patient samples. We have shown recently that hepatitis C virus (HCV) replicons are highly sensitive to IFN-α. In this report we tested whether the replicon system could be used as a sensitive bioassay to determine the amount of biologically active IFN-α in serum or heparinized plasma of patients under therapy. To facilitate the measurements, a stably replicating subgenomic HCV RNA was developed that carries the gene encoding the firefly luciferase. Dose response studies with IFN-α demonstrate that the amount of expressed luciferase directly correlates with the level of HCV replication. By using this cell-based assay, serum samples of HCV patients treated with different types and doses of IFN-α were analyzed in parallel to IFN-α standards made by serial dilutions of the same type of IFN-α the patient was treated with. Based on nonlinear logistic models serum concentrations corresponding to 1.3–19 U/ml were determined in patients under standard or high dose IFN-α therapy, and from 3.8 to 4.1 ng/ml in patients treated with PEG IFN-α. In conclusion, the HCV-replicon based bioassay allows determining the levels of biologically active IFN-α in serum and heparinized plasma of patients under treatment. [Copyright &y& Elsevier]
- Subjects :
- *HEPATITIS C
*INTERFERONS
Subjects
Details
- Language :
- English
- ISSN :
- 01660934
- Volume :
- 110
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Virological Methods
- Publication Type :
- Academic Journal
- Accession number :
- 9908223
- Full Text :
- https://doi.org/10.1016/S0166-0934(03)00134-4