Differences in Viral Dynamics between Genotypes 1 and 2 of Hepatitis C Virus

Many studies have shown that patients infected with hepatitis C virus (HCV) of genotype 2 have better response to interferon (IFN)-α treatment than genotype 1 patients; however, the mechanisms responsible for this difference are not understood. In this study, viral dynamics during high-dose IFN indu...

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Bibliographic Details
Published in:The Journal of infectious diseases 2000-07, Vol.182 (1), p.28-35
Main Authors: Neumann, Avidan U., Lam, Nancy P., Dahari, Harel, Davidian, Marie, Wiley, Thelma E., Mika, Brian P., Perelson, Alan S., Layden, Thomas J.
Format: Article
Language:English
Subjects:
Antiviral Agents - therapeutic use
Apoptosis
Biological and medical sciences
Dosage
Female
Fundamental and applied biological sciences. Psychology
Genetics
Genotype
Genotypes
Hepacivirus
Hepacivirus - genetics
Hepacivirus - physiology
Hepatitis C
Hepatitis C - drug therapy
Hepatitis C - immunology
Hepatitis C - pathology
Hepatitis C - virology
Hepatitis C virus
Humans
Immunomodulators
Infections
Interferon-alpha - therapeutic use
Interferons
Kinetics
Major Articles
Male
Medical sciences
Metabolic Clearance Rate
Microbiology
Middle Aged
Models, Theoretical
Pharmacology. Drug treatments
RNA
RNA, Viral - metabolism
Virions
Virology
Viruses
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Summary:Many studies have shown that patients infected with hepatitis C virus (HCV) of genotype 2 have better response to interferon (IFN)-α treatment than genotype 1 patients; however, the mechanisms responsible for this difference are not understood. In this study, viral dynamics during high-dose IFN induction treatment were compared between the genotypes. Patients in each group received 10 MU of IFN-α2b for 14 days, and HCV RNA levels were frequently determined. Nonlinear fitting, both individually for each patient and using a mixed-effects approach, of the viral kinetic data to a mathematical model of the IFN effect on HCV infection was performed. The antiviral effectiveness of IFN in blocking virus production, the free virion clearance rate, and the HCV-infected cell death rate were all significantly higher for genotype 2 patients than for genotype 1 patients. Thus, the better response rate of patients infected with HCV genotype 2 is multifactorial. This is the first finding of a difference in viral dynamics between subtypes of the same virus and demonstrates the importance of subtype-specific virushost-drug interactions.
ISSN:0022-1899
1537-6613
DOI:10.1086/315661