[Structural analysis of the PKR-binding region of HCV 1b samples from patients with chronic hepatitis C and the correlation with IFN-sensitivity].
BACKGROUND
91.5% of all chronic HCV infections are of 1b-type in Hungary. Japanese researchers found a correlation between the outcome of interferon (IFN) therapy and the structure of the PKR-Binding Region (aa: 2209-2274) of the viral NS5A domain, especially a particular subsection of the PKR-BR, the Interferon Sensitivity Determining Region (ISDR: aa 2209-2248). Several international studies could not confirm these findings.


OBJECTIVE
The objectives of this study were 1. to determine the Hungarian prototype of HCV 1b based on the nucleotide sequence analysis of the PKR-BR of HCV 1b samples from patients with chronic hepatitis C; and 2. to investigate the relationship between the phenotypically expressed mutations of ISDR and the response to IFN therapy.


METHODS
Pre-treatment serum samples of 21 chronic hepatitis C patients (13 women, 8 men), infected with HCV 1b and treated with IFN-alpha (3 sustained responders, 18 non-responders), were analysed retrospectively.


METHODS
Nested reverse transcriptase-polymerase chain reaction (RT-PCR) and direct nucleotide sequencing were applied.


RESULTS
1. The dominant Hungarian quasispecies of HCV 1b differs from the Japan HCV 1b-J, the internationally accepted prototype. 2. The results showed significant correlation between the type of ISDR and the interferon response. Mutant type ISDRs (4 > or = amino acid substitutions) have predictive value for sustained response (p = 0.012). 3. The types and locations of substitutions are not characteristic, except that arginine in position 2218 has predictive value for therapy resistance.


CONCLUSIONS
The authors' study results are in accordance with the earlier Japanese findings and confirm the predictive value of pre-treatment nucleotide sequencing in Hungary. Full adaptation of international research results to a Hungarian context should be treated with caution due to the between-countries virus prototype differences.
Gervain
Judit
J
Fejér Megyei Szent György Kórház, Székesfehérvár, I. Belgyógyászat, Hepato-Pancreatologiai Részleg és Virusszerológiai Laboratórium. jgervain@mail.fmkorhaz.hu
Czibula
Agnes
A
Simon
Judit
J
Kalmár
Tibor
T
D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001665:Binding Sites / Q000235:genetics; D005260:Female; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006814:Hungary; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D016896:Treatment Outcome; D019892:eIF-2 Kinase / Q000235:genetics*
D000998:Antiviral Agents; D007372:Interferons; D019892:eIF-2 Kinase