Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence do not predict the response to recombinant interferon-alfa therapy in French patients.
OBJECTIVE
Studies of HCV quasispecies during interferon treatment have shown the selection of resistant clones. Enomoto et al. have defined the interferon sensitivity-determining region in an amino acid stretch of the HCV-1b NS5A region. Patients with a mutant strain before treatment were complete responders, whereas those with wild-type HCV-J strain were resistant to interferon. The same region was studied in HCV isolates of French patients.


METHODS
Forty-three HCV-1b chronically infected patients, consisting of 26 non-responders and 17 complete responders to interferon-alfa treatment (3 MUI tiw for 6 months), were included retrospectively. We directly sequenced the NS5A(2209-2248) HCV region of these patients before treatment. The viral load could be obtained from six complete responders and 15 non-responders.


RESULTS
We detected wild-type and intermediate strains, but only two mutant strains were present. One of them was found in a non-responder. In three complete responders, we found a wild-type strain. The distribution of the various strains was rather different from that found in Japan. Before treatment, the viral load was lower in complete responders (p=0.01).


CONCLUSIONS
Only two mutant strains were detected in our study. This could partially explain the low response rate to interferon treatment of French HCV-1b-infected patients, although the dose regimen was lower than in Japanese studies. Also, wild-type strains were found in some complete responders, and no correlation was determined between the mutation number in the NS5A(2209-2248) region and response to alfa interferon therapy. This may be related to epidemiological differences between HCV-1b strains present in France and those in Japan. Searching for the mutant NS5A pattern before treatment does not appear to be useful in French patients as it is too uncommon.
Khorsi
H
H
Laboratoire de Virologie, Centre Hospitalo-Universitaire d'Amiens, France.
Castelain
S
S
Wyseur
A
A
Izopet
J
J
Canva
V
V
Rombout
A
A
Capron
D
D
Capron
J P
JP
Lunel
F
F
Stuyver
L
L
Duverlie
G
G
D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D005260:Female; D005602:France; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000628:therapy / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012189:Retrospective Studies; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase