Jpn. J. Infect. Dis., 59 (2), 92-99, 2006

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Original Article

Mutations within Protein Kinase R-Binding Domain of NS5A Protein of Hepatitis C Virus (HCV) and Specificity of HCV Antibodies in Pretreatment Sera of HCV-Chronically Infected Patients and Their Effect on the Result of Treatment

Dariusz Kmieciak*, Lukasz Kruszyna, Pawel Migdalski1, Mariusz Lacinski, Jacek Juszczyk1 and Wieslaw H. Trzeciak

Department of Biochemistry and Molecular Biology and 1Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland

(Received November 29, 2005. Accepted February 13, 2006)


*Corresponding author: Mailing address: Karol Marcinkowski University of Medical Sciences, Department of Biochemistry and Molecular Biology, 6 Swiecickiego St., 60-781 Poznan, Poland. Tel: +48-61-8546513, Tel/Fax: +48-61-8546510, E-mail: dkmiec@am.poznan.pl


SUMMARY: We analyzed protein kinase R (PKR)-binding domain sequences of hepatitis C virus (HCV) NS5A protein and the profile of HCV-specific antibodies from pretreatment sera of HCV-chronically infected patients. Results were compared with clinical data to verify their influence on the course and result of therapy. Of 9 patients enrolled in a 12-month treatment with pegylated interferon alpha (PEG-IFN-alpha) plus ribavirin (RBV), 6 patients responded to therapy, as assessed by the lack of HCV RNA in their sera, and 3 did not. Among 8 HCV-1b-infected patients, those who responded did not have significantly more mutations in the IFN sensitivity determining region (ISDR) compared to non-responders (P = 0.637). Similarly, in the remaining 26-amino acid region of the PKR-binding domain, behind ISDR, the number of mutations did not differ significantly between the two groups (P = 0.796). A correlation was found between the presence of envelope 2 (E2)-specific antibodies and the result of treatment (P = 0.048). This pilot study indicates that mutations in the PKR-binding domain of HCV genotype 1b do not correlate with outcome of PEG-IFN-alpha/RBV therapy. However, the presence of E2-specific antibodies in the pretreatment sera of HCV-chronically infected individuals could serve as a prognostic marker predicting the result of treatment, before its initiation.


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