Integrity of the NS5A (amino acid 2209 to 2248) region in hepatitis C virus 1b patients non-responsive to interferon therapy.

Abstract

BACKGROUND/AIMS:

In hepatitis C virus-1b, it has been suggested that an amino acid stretch (aa 2209-2248) of the carboxy terminal half of the non-structural 5A (NS5A) region participates in the response to interferon treatment. We tested the hypothesis that absence of mutations in the NS5A (aa 2209-2248) sequence is required for interferon resistance. We also investigated the importance of different HCV-1b isolates in interferon response in France.

METHODS:

We determined the NS5A sequences of 70 patients with chronic hepatitis C before IFN therapy and then compared them with HCV-J prototype sequence. The isolates were determined by NS5B sequencing, the "gold standard" method for genotyping and subtyping. Pre-therapeutic viral load was also measured.

RESULTS:

No sustained virological response was observed in the patients without amino acid substitutions in the NS5A (aa 2209-2248) sequence, and in the patients with HCV-J isolates. Viral load was significantly higher in the patients with no amino acid substitutions in the NS5A (aa 2209-2248) sequence.

CONCLUSIONS:

In HCV-lb infected patients, an HCV-J strain with no amino acid substitution in the NS5A (aa 2209 2248) region indicates a poor prognosis for response to IFN therapy. The low interferon response rate in HCV-lb infection in Europe is probably not due to a difference between isolates.

• Authors: P Halfon, G Halimi, M Bourlière, D Ouzan, J Durant, H Khiri, L Mercier, V Gerolami, G Cartouzou
• Journal: Liver (Liver) Vol. 20 Issue 5 Pg. 381-6 (Oct 2000) ISSN: 0106-9543 [Print] Denmark
• PMID: 11092256 (Publication Type: Journal Article)

Chemical References

• RNA, Viral
• Viral Nonstructural Proteins
• Interferons
• Alanine Transaminase
• NS-5 protein, hepatitis C virus

Topics

• Alanine Transaminase (blood)
• Amino Acid Sequence
• Amino Acid Substitution (genetics)
• Drug Resistance (genetics)
• Genes, Viral (genetics)
• Genotype
• Hepacivirus (chemistry, genetics, physiology)
• Hepatitis C, Chronic (drug therapy, genetics)
• Humans
• Interferons (pharmacology, therapeutic use)
• Molecular Sequence Data
• Mutation (genetics)
• RNA, Viral (analysis, blood)
• Sequence Alignment
• Sequence Analysis, Protein
• Viral Load
• Viral Nonstructural Proteins (chemistry, genetics, metabolism)