Why is the interferon sensitivity-determining region (ISDR) system useful in Japan?
OBJECTIVE
The amino acid sequence of NS5A2209-2248, named the "interferon sensitivity-determining region" (ISDR), has been reported to correlate with responsiveness of interferon (IFN) therapy to patients with the hepatitis C virus (HCV) genotype-1b, by several Japanese authors. However, European authors have failed to find this phenomenon, suggesting a difference in HCV-1b isolates between Japan and Europe.


METHODS
We compared the HCV-1b nucleotide sequences of our Japanese patients and those of other countries quoted from GenBank, using the envelope 1 sequence.


RESULTS
A phylogenetic tree analysis revealed two characteristic groups from a geographical viewpoint: one group (NJ group) consists of almost entirely non-Japanese isolates, and the other (J group) of almost entirely Japanese isolates. The isolates other than the NJ and J groups are characterized by their specific nucleotide residue, constructing an individual group (W group). Japanese HCV-1b isolates consist of the J group and W group (approximately 40% and 60%, respectively). Comparative study between the two groups in Japanese patients treated with IFN revealed a strong correlation between ISDR type and IFN responsiveness only in the J group, but not in the W group.


CONCLUSIONS
These observations convinced us that the existence of the Japan-specific J group is one reason why the ISDR system is useful only in Japan.
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
I
I
Nakano
Y
Y
Fukuda
Y
Y
Katano
S
S
Nakano
T
T
Kumada
T
T
Hayakawa
D001483:Base Sequence; D005060:Europe; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007564:Japan; D012324:RNA-Dependent RNA Polymerase / Q000032:analysis*; D017361:Viral Nonstructural Proteins / Q000032:analysis*
D017361:Viral Nonstructural Proteins; D007372:Interferons; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase