Effect of increasing dose of interferon on the evolution of hepatitis C virus 1b quasispecies.
The effects of interferon therapy on hepatitis C virus (HCV) genome are still controversial in terms of biological and clinical significance. Changes in the quasispecies of the hypervariable (HVR) and non-structural 5A (NS5A) regions of HCV 1b were evaluated in nine patients treated with increasing doses of interferon and five untreated controls. HCV quasispecies were analyzed in HVR and NS5A by single-strand conformation polymorphism assay. The HVR quasispecies varied over time both in treated and untreated patients. However, at least one persistent strain was present in all patients. With low doses of interferon, variations in HVR complexity were found in seven of nine patients and in four patients new variants became detectable. A reduction in the heterogeneity of the HVR quasispecies was observed after increase of the interferon dose. In contrast, NS5A profiles remained unmodified in all but three cases in which direct sequencing showed no changes in amino acid sequences of the predominant strain. The results suggest that interferon sensitivity of some HCV strains may be dose dependent. The homogeneity of NS5A pattern populations during treatment suggests that interferon exerts much less pressure on this region.
De Mitri
M S
MS
Department of Internal Medicine, Cardioangiology, Hepatology; University of Bologna, Italy.
Mele
L
L
Morsica
G
G
Chen
C H
CH
Sitia
G
G
Gramenzi
A
A
Andreone
P
P
Alberti
A
A
Bernardi
M
M
Pisi
E
E
D020121:5' Untranslated Regions / Q000032:analysis; D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000628:therapy / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017386:Sequence Homology, Amino Acid; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D020121:5' Untranslated Regions; D000998:Antiviral Agents; D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C400562:HVR1 protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase