Identification of hepatitis C virus (HCV) subtype 1b strains that are highly, or only weakly, associated with hepatocellular carcinoma on the basis of the secondary structure of an amino-terminal portion of the HCV NS3 protein.
The NS3 protein of hepatitis C virus subtype 1b (HCV-1b) isolates obtained from 89 patients with hepatocellular carcinoma (HCC) and 78 patients without HCC were analyzed. On the basis of the secondary structure of the amino-terminal 120 residues of NS3, HCV-1b isolates were classified into group A, group B, and an indeterminate group, each of which was further divided into a number of subgroups, such as A1-1, A1-2, A2-1, A2-2, B1-1, B1-2, B2-1, B2-2, C-1, C-2, and C-3. HCV-1b isolates of subgroup B1-1 were found in 53 (59.6%) of 89 patients with HCC and 19 (24.4%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.00001). Although the number of isolates was small, subgroup B2-1 was also highly associated with HCC, with all five isolates in that subgroup being found in patients with HCC (P < 0.05). On the other hand, HCV-1b isolates of subgroup A1-1 were associated only weakly with HCC; they were found in 6 (6.7%) of 89 patients with HCC and in 25 (32.1%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.0001). The other subgroups, such as A1-2, A2-1, B1-2, C-1, C-2, and C-3, were moderately associated with HCC; their distribution patterns among patients with HCC did not differ significantly from those among patients without HCC. Taken together, our results suggest that HCV-1b isolates of subgroups B1-1 and B2-1 are highly associated with HCC and that this secondary structure analysis may be useful for predicting the relative risk of developing HCC.
Ogata
Satoshi
S
Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Florese
Ruth Huab
RH
Nagano-Fujii
Motoko
M
Hidajat
Rachmat
R
Deng
Lin
L
Ku
Yonson
Y
Yoon
Seitetsu
S
Saito
Takafumi
T
Kawata
Sumio
S
Hotta
Hak
H
D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D005260:Female; D016174:Hepacivirus / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases