Restriction of hepatitis C virus heterogeneity during prolonged interferon-alpha therapy in relation to changes in virus load.
To determine how interferon-alpha (IFN-alpha) treatment changes the heterogeneity of the hepatitis C virus (HCV) population, the hypervariable region 1 (HVR1) was directly sequenced, and the virus load was quantified in 15 patients who had received IFN-alpha for 15 months. Before treatment, 13 patients exhibited heterogeneous HVR1 sequences. In 7 subjects who did not respond or did not sustain a response to treatment, significantly decreased heterogeneity of the HVR1 was found at the end of treatment (P=.01). In 6 of these patients, the virus load decreased in parallel with the changes in HVR1 heterogeneity. At follow-up, both the virus load and the heterogeneity increased in 4 patients, and the virus load, but not the heterogeneity, increased in 2. In the seventh patient, the virus load steadily increased during treatment and follow-up. These results suggest that a selection of HVC strains may occur during prolonged IFN-alpha treatment, concomitant with general suppression of the viral replication.
Yun
Z B
ZB
Karolinska Institute, Huddinge University Hospital, Sweden.
Odeberg
J
J
Lundeberg
J
J
Weiland
O
O
Uhlen
M
M
Sonnerborg
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008969:Molecular Sequence Data
D017931:DNA Primers; D004279:DNA, Viral; D016898:Interferon-alpha