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)-alpha 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-alpha2b 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 virus-host-drug interactions.
Neumann
A U
AU
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel. neumann@mail.biu.ac.il
Lam
N P
NP
Dahari
H
H
Davidian
M
M
Wiley
T E
TE
Mika
B P
BP
Perelson
A S
AS
Layden
T J
TJ
D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008962:Models, Theoretical; D012367:RNA, Viral / Q000378:metabolism
D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral