In:
Antiviral Therapy, SAGE Publications, Vol. 11, No. 4 ( 2006-05), p. 507-519
Abstract:
Formation of transmembrane ion channels by hepatitis C virus (HCV) p7 and abrogation of channel function by amantadine was demonstrated in vitro. The relevance of HCV p7 amino acid (aa) variations for response to antiviral therapy with amantadine is unknown. Methods HCV p7 was sequenced in 86 individuals who were infected with HCV genotype 1. Thirty-six of 86 patients received amantadine within an interferon-α (IFN-α)-based antiviral therapy. Helical wheel modelling for HCV p7 was performed. Results No significant correlation of overall aa variations within HCV p7 was observed with response to IFN-α-based therapy with amantadine in HCV genotype 1a/b infected patients. When analysis was restricted to non-conservative aa variations, a higher number of aa substitutions within complete HCV p7 and transmem-brane helix 2 was associated with non-response in HCV-1b-infected patients receiving therapy with amantadine ( P=0.015 and P=0.037, respectively), without amantadine ( P=0.106 and P=0.118, respectively), and in the total cohort of HCV-1b-infected patients ( P=0.00007 and P=0.011, respectively). Furthermore, substitution L20F was observed more often in non-responders than responders with HCV-1b infection and therapy with amantadine ( P=0.099). By in silico modelling, aa 20 was located toward the p7 channel lumen. Substitution L20F may impair amantadine action by altering the shape of the ion channel pore. Conclusion Substitution L20F within HCV p7 may be associated with non-response to combination therapy specifically with amantadine in HCV-1b-infected patients. Non-responders with HCV-1b infection showed higher numbers of non-conservative aa variations within HCV p7 than responders, irrespective of the application of amantadine.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
DOI:
10.1177/135965350601100408
Language:
English
Publisher:
SAGE Publications
Publication Date:
2006
detail.hit.zdb_id:
2118396-X
SSG:
15,3
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