Nucleotide sequence diversity of hypervariable region 1 of hepatitis C virus in Japanese hemophiliacs with chronic hepatitis C and patients with chronic posttransfusion hepatitis C.
Hemophiliac patients with chronic hepatitis C might be exposed to and become infected with multiple hepatitis C virus (HCV) strains by means of frequent use of blood products, even if they are infected with a single subtype of HCV. To test this hypothesis, we analyzed the genetic diversity of hypervariable region 1 (HVR1) of HCV in chronically infected hemophiliacs and in patients with chronic posttransfusion hepatitis with a single HCV inoculation. The diversity of nucleotide sequences in HVR1 of serum HCV RNA was compared between 21 hemophiliacs infected with a single HCV subtype and 16 patients with posttransfusion HCV infection. The number of HCV quasispecies was determined by fluorescence single-strand conformation polymorphism (SSCP) analysis. Direct sequencing was performed to determine the diversity in HVR1. The number of HCV quasispecies in the blood was 5.2 +/- 2.0 clones in hemophiliacs and 4.0 +/- 2.3 clones in posttransfusion patients, a nonsignificant difference (P = .0943). The number of sites at which the nucleotide was not homogenous in all quasispecies was significantly higher in hemophiliacs (13.0% +/- 7.4%) than in posttransfusion hepatitis patients (2.7% +/- 2.8%; P < .0001). In conclusion, there was a high degree of genetic variation in HVR1 of HCV specimens isolated from hemophiliacs compared with posttransfusion patients. These findings indicate the possibility that multiple infections of a single HCV subtype may occur among patients frequently exposed to blood products; single HCV subtypes may therefore derive from multiple origins.
Toyoda
H
H
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Fukuda
Y
Y
Koyama
Y
Y
Nakano
I
I
Kinoshita
M
M
Hadama
T
T
Takamatsu
J
J
Hayakawa
T
T
D000328:Adult; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006467:Hemophilia A / Q000150:complications; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000382:microbiology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000235:genetics*; D065227:Transfusion Reaction
D017931:DNA Primers; D012367:RNA, Viral