Integrity of the NS5A (amino acid 2209 to 2248) region in hepatitis C virus 1b patients non-responsive to interferon therapy.
OBJECTIVE
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.
Halfon
P
P
Laboratoire Alphabio, Hôpital de la Conception, Marseilles, France. alphabio@wanadoo.fr
Halimi
G
G
Bourlière
M
M
Ouzan
D
D
Durant
J
J
Khiri
H
H
Mercier
L
L
Gerolami
V
V
Cartouzou
G
G
D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
D000410:Alanine Transaminase; D007372:Interferons; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase