Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1993-03-18
1999-03-09
Scheiner, Laurie
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
435 693, 435 711, 435235, 4352523, 4353201, 536 231, 536 2372, C07H 2104, A61K 3100
Patent
active
058799044
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to nucleotide and peptide sequences of a European, more particularly French, strain of the hepatitis C virus, as well as to the diagnostic and therapeutic applications of these sequences.
The hepatitis C virus is a major causative agent of infections by viruses previously called "Non-A Non-B" viruses. Infections by the C virus in fact now represent the most frequent forms of acute hepatitides and chronic Non-A Non-B hepatitides (Alter et al. (1), Choo et al., (3); Hopf et al., (5); Kuo et al., (8); Miyamura et al., (11). Furthermore, there is a relationship (the significance of which is still poorly understood) between the presence of anti-HCV antibodies and the development of primary liver cancers. It has also been shown that the hepatitis C virus is involved in both chronic or acute Non-A Non-B hepatitides linked to transfusions of blood products or of sporadic origin.
The genome of the hepatitis C virus has been cloned and the nucleotide sequence of an American isolate has been described in EP-A-0 318 216, EP-A-0 363 025, EP-A-0 388 232 and WO-A-90/14436. Moreover, data is currently available on the nucleotide sequences of several Japanese isolates relating both to the structural region and the nonstructural region of the virus (Okamoto et al., (12), Enomoto et al., (4), Kato et al., (6); Takeuchi et al., (15 and 16)). The virus exhibits some similarities with the group comprising Flavi- and Pestiviruses; however, it appears to form a distinct class, different from viruses known up until now (Miller and Purcell, (10)).
In spite of the breakthrough which the cloning of HCV represented, several problems persist: which has made it possible to describe the existence of two groups of viruses, possibility of detecting anti-HCV antibodies in the serum of patients. This is due to the existence of false positive results and to a delayed seroconversion following acute infection. Finally there are clearly cases where only the detection of the virus RNA makes it possible to detect the HCV infection while the serology remains negative.
These problems have important implications both with respect to diagnosis and protection against the virus.
The authors of the present invention have carried out the cloning and obtained the partial nucleotide sequence of a French isolate of HCV (called hereinafter HCV E1) from a blood donor who transmitted an active chronic hepatitis to a recipient. Comparison of the nucleotide sequences and the peptide sequences obtained with the respective sequences of the American and Japanese isolates showed that there was
The present invention is based on new nucleotide and polypeptide sequences of the hepatitis C virus which have not been described in the abovementioned state of the art.
The subject of the present invention is thus a DNA sequence of HCV E1 comprising a DNA sequence chosen from the nucleotide sequences of at least 10 nucleotides between the following nucleotides (n); n.sub.118 to n.sub.138 ; n.sub.177 to n.sub.202 ; n.sub.233 to n.sub.247 ; n.sub.254 to n272 and n.sub.272 to n.sub.288 represented in the sequence SEQ ID NO:2, and, n.sub.156 to n.sub.170 ; n.sub.170 to n.sub.217 ; n.sub.267 to n.sub.263 and n.sub.310 to n.sub.334 represented in the sequence SEQ ID NO:4; as well as analogous nucleotide sequences resulting from degeneracy of the genetic code.
The subject of the invention is in particular the following nucleotide sequences: SEQ ID NO:2, SEQ IS NO:4 and SEQ ID NO:6.
The oligonucleotide sequences may be advantageously synthesised by the Applied Bio System technique.
The subject of the invention is also a peptide sequence of HCV E1 comprising a peptide sequence chosen from the sequences of at least 7 amino acids between the following amino acids (aa): aa.sub.58 to aa.sub.66 ; aa.sub.76 to aa.sub.101 represented in the peptide sequence SEQ ID NO:3; aa.sub.49 to aa.sub.78 ; aa.sub.98 to aa.sub.111 ; aa.sub.123 to aa.sub.133 ; aa.sub.140 to aa.sub.149 represented in the peptide sequence SEQ ID NO:5; as well as homologous peptide sequences whic
REFERENCES:
Choo et al, Science, vol. 244, 21 Apr. 1989, pp. 359-362, "Kolation of a cDNA Clone Derived from a Blood-Borne Non-A, Non-B Viral Hepatitis Genome".
Weiner et al, Virology, vol. 180, 1991, pp. 842-848, "Variable and Hypervariable Domains are Found in the Regions of HCV Corresponding to the Flavivirus Envelope and NS1 Proteins and the Pesvirus Envelope Glycoproteins".
Norio Ogata et al., Proc. Natl. Acad. Sci. USA, vol. 88, pp. 3392-3396, Apr. 1991, "Nucleotide sequence and mutation rate of the H strain of hepatitis C virus".
Okamoto et al., Japan J. Exp. Med., vol. 60, No. 3, 1990, pp. 167-177.
Weiner et al., Virology, vol. 180, No. 2, Feb. 1991, pp. 842-848.
Brechot Christian
Kremsdorf Dina
Porchon Colette
Institut Pasteur
Scheiner Laurie
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