Molecular cloning of HCV and clinical application.
Fifty-five clones encoding epitopes of HCV were isolated from Japanese patients. Their amino acid homology (AAH) to the sequence of prototype (HCV-1) ranged from 47% to 94%. These sequences cover 60% of the HCV genome lacking M/E and NS2 regions suggesting a very low or lacking immunogenicity for these regions. Two test kits for detection of anti-HCV antibody were developed using a combination of a synthetic peptide (AR142) containing the epitope of N14 (QRKTKRSTNRR) having a homology to the core of HCV of 8/11AA and a non-fusion recombinant protein Y19 starting from amino acid number (AAN) 1380 to 1507 in the NS3 region showing a AAH to the HCV-1 of 90%, and a combination of a mixture of three synthetic peptides of S29 AAN of 1-30, 38-65 and 47-74 of the core and a non-fused recombinant protein S4 AAN of 1287-1506 having a 93% AAH of the NS3 region. They showed almost the same order of sensitivity and specificity of the second-generation kits when tested with serum from blood donors and patients with non-A, non-B hepatitis. It should also be stressed that in all of the complete responders of a recombinant alpha-interferon therapy, the antibody levels against AR142 gradually decreased during and after the treatment. In 1992, studies performed for 125 patients with hepatocellular carcinoma in our clinic shows that of these 16 patients might developed from either chronic non-B, non-C liver diseases or chronic liver diseases caused by mutant(s) of HCV as their serum were negative for HBsAg and second-generation of anti-HCV.
Arima
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Second Department of Internal Medicine, Kagoshima University, Japan.
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002213:Capsid / Q000276:immunology*; D002648:Child; D003001:Cloning, Molecular; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000097:blood*; D018937:Hepatitis C Antibodies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology*
D006508:Hepatitis Antibodies; D018937:Hepatitis C Antibodies; D011993:Recombinant Fusion Proteins