Relationship of hepatitis C genotype 1 NS5A sequence mutations to early phase viral kinetics and interferon effectiveness.
Publication/Presentation Date
4-1-2002
Abstract
The interferon (IFN) sensitivity-determining region (ISDR) of the hepatitis C virus (HCV) NS5A protein is controversially implicated in determining IFN-alpha-sustained viral response for HCV genotype 1-infected patients. Because the NS5A protein interferes with protein kinase antiviral activity, this study attempted to determine whether ISDR amino acid mutation number would correlate better with IFN effectiveness to inhibit virus production and elicit early virus clearance. Early viral kinetic data from 22 genotype 1-infected patients treated with high-dose IFN was compared with ISDR mutation number. IFN effectiveness and first-phase viral log decline correlated directly with ISDR mutation number (P=.02). Mean mutation number was higher among rapid responders (3.7+/-1.0; n=6) than among nonresponders (1.3+/-1.0; n=16) (P=.001). Also, second-phase viral log decline and calculated hepatocyte death rate correlated directly with ISDR mutation number (P=.01). This supports a dual effector role for NS5A, which regulates virus production and immune clearance early in therapy.
Volume
185
Issue
7
First Page
868
Last Page
877
ISSN
0022-1899
Published In/Presented At
Schiappa, D. A., Mittal, C., Brown, J. A., & Mika, B. P. (2002). Relationship of hepatitis C genotype 1 NS5A sequence mutations to early phase viral kinetics and interferon effectiveness. The Journal of infectious diseases, 185(7), 868–877. https://doi.org/10.1086/339485
Disciplines
Psychiatry
PubMedID
11920310
Department(s)
Department of Psychiatry
Document Type
Article