Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1994-02-10
1999-09-14
Caputa, Anthony C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 231, 536 2432, 435 693, C12N 1537, C07N 2104
Patent
active
059524871
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The invention relates to specific DNA sequences derived from the genome of papillomavirus HPV42, including the sequence corresponding to its entire genome, as well as recombinant DNAs, in particular vectors containing all or part of those DNA sequences which code for structural proteins of these papillomaviruses or parts of these proteins. The invention also relates to the cell cultures transformed by the said recombinant DNAs under conditions optionally enabling them to express the corresponding sequences derived from the HPV42 genome in the form of the corresponding proteins. Finally, the invention relates to diagnostic kits making use of some of the products defined above or those whose description follows and their novel uses, more particularly for the discrimination between benign genital epithelial lesions and lesions of the carcinoma or pre-carcinoma type induced by papillomaviruses.
Most of the 60 or more different types of human papillomaviruses hitherto identified are all epitheliotropic viruses presumed to be responsible for the induction of an abnormal growth of the infected tissue (1, 39). Depending on their tissue specificities and respective predominance in benign or malignant tumors, the types of human papillomaviruses (HPV) have been classed in different groups, for example low risk groups (HPV 6, 11) (2, 3), high-risk groups (HPV 16, 18, 31, 33, 39, 57) (1, 4-8), genital HPVs and HPVs associated with epidermodysplasia verruciformis (HPV 5, 8, 19, 25, 47) (1, 9-11), etc. . With the objective of gaining a better understanding of their mutual relationship and, if necessary, of revealing the nature of their tissue specificities, it has also been suggested that sequence comparisons be made. However, attempts to establish correlations between certain characteristics of the virus and certain specific characteristics of their respective genomes have not really proved to be successful up to now. The demonstration of the difficulty of establishing such correlations is illustrated particularly by the result of the sequence studies which have been conducted on papillomavirus HPV42, which had already been isolated from vulvar papillomas, by the use of a DNA of the oral HPV32 type (12) as probe under conditions of low stringency (13). According to this last publication HPV42 proved to be present in 3.5% of the genital lesions which in most cases exhibited histological characteristics of condylomas or flat papillomas.
SUMMARY OF THE INVENTION
The invention is also based on the discovery of specific sequences present in HPV42, sequences which form the basis of its originality and which allow particularly discriminating detections of papillomaviruses of the HPV42 type and confirmation (or refutation) of results of in vitro diagnoses performed with probes containing DNA sequences derived from other papillomaviruses. These sequences or fragments of these sequences can also be used to constitute particularly sensitive hybridization probes, in particular primers which make possible analyses by the so-called PCR method.
In what follows use will be made of some abbreviations derived from English expressions. They are conserved in the text to facilitate the reading of the text by specialists who are used to these abbreviations.
They are given below, and are followed by the complete English: expressions from which they derive
Before proceeding further with the description of these sequences or sequence fragments, it is proposed to make a brief review of the state of the prior art and then to provide a detailed description of the HPV42 genome.
BRIEF DESCRIPTION OF THE DRAWINGS
The remainder of the description will be given with reference to the appended figures, the legends to which are the following:
FIG. 1: 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i) (SEQ ID NO: 1: Nucleotide sequence of the DNA strand of HPV42 analogous to the mRNA. Position 1 on the circular genome was determined by alignment with positions 1 of HPV11 and HPV39.
First nucleotides: +1, +1801, +3601 an
REFERENCES:
Philipp, Wolfgang, et al., "Human Papillomavirus Type 42: New Sequences, Conserved Genome Organization," Virology 186:331-334 (1992).
Bowie et al. Science 247:1306-1310, Mar. 1990.
Kumar et al. PNAS 87:1337-1341, Feb. 1990.
Munger et al. EMBO Journal 8(13):4099-4105 1989.
Beaudenon et al. Virology 161:387-384 1987.
Cole Stewart
Honore Nadine
Philipp Wolfgang
Sapp Martin
Caputa Anthony C.
Hayes Robert C.
Institut Pasteur
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