HCV diagnostic agents

Details HCV diagnostic agents HCV diagnostic agents

1995-10-24

1999-06-08

Woodward, Michael P.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving virus or bacteriophage

435 71, 435 693, 530300, 530324, 530350, 530811, 530826, C12Q 170, G01N 3353, C07K 1418

Patent

active

059104058

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to hepatitis C virus(HCV)-specific epitopes, recombinant proteins comprising one or more of the HCV epitopes and a process for detecting antibodies against hepatitis C virus in a putative serum sample by using said recombinant proteins. More particularly, it pertains to epitopes of HCV core protein and non-structural 3 protein(NS3), and a recombinant protein comprising the same, epitopes of HCV envelope protein and Non-structural 4 protein, and a recombinant protein comprising the same, and epitopes of HCV non-structural 5 protein and a recombinant protein comprising the same; processes for producing the recombinant proteins; an agent for diagnosing antibodies against hepatitis C virus in a putative serum sample, which comprises said recombinant proteins; and a process for diagnosing hepatitis C by using the agent.


BACKGROUND OF THE INVENTION

Hepatitis C virus(HCV) is a primary cause of viral hepatitis which progresses into cirrhosis or hepatocellular carcinoma, and it has been reported that about 70 to 80% of hepatitis caused by blood transfusion is due to said virus(Alter, H. J., et al., Lancet, 2, 838-841(1975); and Dienstag, J. L., et al., Seminar Liver Dis., 6, 67-81(1986)). Said virus is one of RNA viruses consisting of one positive RNA strand and produces a polyprotein precursor from an open reading frame(ORF) of the strand(Choo, Q. L., et al., Science, 244, 359-362(1989); and, Choo, Q. L., et al., Proc. Natl. Acad. Sci. USA, 88, 2451-2455(1991)).
The gene structure of hepatitis C virus is similar to that of flavivirus or pestivirus(Miller, R. H., et al., Proc. Natl. Acad. Sci. USA, 87, 2057-2061(1990); and, Muraiso, K., et al., Biochem. Biophys. Res. Commun., 172, 511-516(1991)), and on the basis of said relationship it is presumed that the polyprotein of hepatitis C virus consists of, from N-terminal to C-terminal, core-envelope 1(E1)-envelope 2
on-structural 1 protein(E2/NS1)-non-structural 2 protein(NS2)-non-structural 3 protein(NS3)-non-structural 4 protein(NS4)-non-structural 5 protein(NS5)(Choo, Q. L., et al., Proc. Natl. Acad. Sci. USA, 88, 2451-2455(1991); Takamizawa, A., et al., J. Virol., 65, 1105-1113(1991); and Kato, N., et al., Proc. Natl. Acad. Sci. USA, 87, 6524-6528(1990)).
The infection of hepatitis C virus can be diagnosed by detecting hepatitis C viral RNA directly from a blood sample by using polymerase chain reaction(PCR)(Hosoda, K., et al., Hepatology, 15, 777-781(1992); Abe, K., et al., Hepatology, 15, 690-695(1992); and, Alter, H. J., Annals of Internal Medicine, 115, 644-649(1991), whereby the viral RNA can be detected rather early, i.e., within 1 to 2 weeks from the infection; however, such method entails high cost and long time due to the need to analyze numerous samples. Another diagnostic method is to detect antibodies against hepatitis C virus present in the serum sample, e.g., by an enzyme-linked immunoassay using C100-3 protein(see Houghton et al., PCT WO 89/04669; WO 90/11089). Kuo et al. disclosed in Science 244, 362-384(1989) that more than 70% of patients with post-transfusion hepatitis have antibodies against the C100-3 protein.
However, said C100-3 antigen used as an active ingredient for the diagnostic agents reacts only to the antibodies of patients with chronic hepatitis C, not with those of patients with acute hepatitis C at its early stage since the antibodies are not generally produced until 4 to 6 months after the HCV infection. As a result, it often exhibits a false negative during the early stage of the disease(Alber, H. J., et al., N. Engl. J. Med., 321, 1494-1500(1989); Myamura, T., et al., Proc. Natl. Acad. Sci. USA, 87, 983-987(1990)); and, further, it often exhibits false positive results in a considerable proportion in the case of hepatitis caused by the autoimmune disease of the patients and not by HCV(McFarlane, I. G., et al., Lancet, 335, 754-757(1990)).
Okamoto et al. disclosed the nucleotide sequences of the cDNA clones including the 5'-terminal region and structural genes encoding th

REFERENCES:
patent: 5574132 (1996-11-01), Lacroix
Chang et al., 1991, Mol. Cells 1:507-10.

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