Detection of mammalian immunodeficiency viruses

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage

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435 693, 435975, 530324, 530328, C12Q 170, C07K 1415

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055915728

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BRIEF SUMMARY
This invention relates to methods of detection of mammalian immunodeficiency viruses, and in particular to peptides suitable for use in immunoassays for the detection of antibodies to such viruses.


BACKGROUND AND RELATED ART

Since the recognition of human acquired immunedeficiency syndrome (AIDS) in 1981, there has been intensive research into the causal virus, human immunodeficiency virus (HIV), formerly known as human T-cell lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). It is now known that HIV-specific antibodies are present in the sera not only of most patients with AIDS or AIDS-related complex, but also in the sera of asymptomatic individuals exposed to the virus.
More recently, a variant virus, known as HIV-2, has also been found to be capable of causing AIDS. Immunoassay methods, such as ELISA, utilising various polypeptides encoded by the HIV virus have been extensively used in diagnosis and screening. In most cases the polypeptides are either directly prepared from viral material, or are derived from in vitro expression systems using recombinant DNA technology, although such materials are not ideal. Material derived from viral preparations may be contaminated by viable virus, thus posing a hazard to personnel using the material. Recombinant-derived material may be contaminated by non-HIV protein, resulting in possible loss of specificity.
In an attempt to overcome this problem, polypeptides of HIV have been produced using chemical synthetic means; peptide fragments of a variety of HIV-antigens are disclosed in Australian Patent Application No. 597884 (57733/86) by Genetic Systems Corporation, and in U.S. Pat. Nos. 4,735,896 and 4,879,212, both by United Biomedical Inc. In particular, these three specifications disclose a conserved immunodominant region of gp41 glycoprotein, a region of the major envelope protein of HIV-1. An analogous region of the gp36 protein of HIV-2 has also been synthesised. These regions, which correspond to the transmembrane portion of the envelope protein, enable preferential diagnosis of HIV-1 and HIV-2, and provide assays of very high sensitivity and specificity.
Research on retroviral infections, and in particular those associated with immunodeficiency diseases, has shown that immunodeficiency viruses are widespread among mammalian species. For example, Simian immunodeficiency viruses (SIV strains) have been found in a variety of Old World monkey and ape species, such as macaques, gibbons, and chimpanzees. Similar viruses have been found to infect bovids (bovine immunodeficiency virus, BIV), and felids (feline immunodeficiency virus, FIV). FIV is a retrovirus originally isolated from domestic cats, and has been shown to belong to the same group as HIV (Pederson, N. C. et al; Science (1987) 235 790). This virus has been found in domestic cats in all countries tested, and is associated with similar conditions to those found in AIDS patients; however, the infections seen are only those which normally occur in domestic cats. Fungal infections, such as cryptococcosis, are particularly common, and respond well to symptomatic treatment. Although FIV does not lead to catastrophic infections such as those seen in humans with HIV, and although the virus appears to have been present in the feline population for at least 20 years before its discovery, infection is very widespread and causes significant distress and suffering. There may be other long term implications.
For example, it has recently been found that FIV antibody is widespread in big cats, such as lions, jaguars, leopards and pumas, both in zoo populations and in free ranging animals (Barr M. C., Calle P. R. et al; J. Zoo and Wildlife Med. (1989) 20 285; Sabine M. and Walker C.; Today's Life Science, 1991 3 34). Although in the Australian study by Sabine and Walker contact between the zoo animals and domestic cats could not be ruled out, the zoo cats in the United States in the study by Barr and Calle et al had no contact either with domestic cats or with other infected exotic cats

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