Mutations in interferon sensitivity-determining region of hepatitis C virus: its relation to change in viral load.
OBJECTIVE
Interferon sensitivity-determining region (ISDR) in nonstructural region 5A of hepatitis C virus (HCV) genotype-1b has been reported to be associated with viral load. Viral load is usually small in the patients with mutant type (four or more amino acid substitutions, compared with HCV-J) and large in those with wild (identical to HCV-J) or intermediate type (from one to three amino acid substitutions). A possible correlation was investigated between mutations in ISDR and alterations of viral load during the course of disease.


METHODS
The sequences of ISDR were determined in eight patients with significant changes of viral load and in 11 patients without changes.


RESULTS
In two of the eight patients with significant alterations of viral load, ISDR sequences changed significantly. In one patient whose viral load increased after a course of interferon therapy, the number of substitutions, compared with HCV-J, decreased from five to zero or one; the type of ISDR converted from mutant type to wild or intermediate type. In one patient whose viral load decreased significantly after two courses of interferon therapy, the number of substitutions increased from one to six; ISDR changed from intermediate type to mutant type. In the remaining six patients with changes of viral load and in the other 11 patients without changes, the sequences of ISDR did not change significantly.


CONCLUSIONS
The mutations in ISDR are one of the viral factors involved in the changes in viral load during the course of disease, although the majority of other factors involved are still unknown.
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Y
Y
Terazawa
K
K
Yoshioka
M
M
Kobayashi
K
K
Watanabe
M
M
Ishigami
M
M
Yano
K
K
Takagi
S
S
Kakumu
D000328:Adult; D000595:Amino Acid Sequence; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000097:blood* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D019562:Viral Load
D007372:Interferons