Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1998-05-14
2000-12-05
Salimi, Ali
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
4352351, 435 9133, 43537633, C12Q 170, C12P 1934, C12N 700
Patent
active
061564982
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a lymphoma cell line capable of producing large quantities of Kaposi's sarcoma-associated herpes virus (KSHV or HHV-8), which are substantially free from human immunodeficiency virus (HIV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). This invention also relates to the purified virus produced thereby, and to methods for establishing HHV-8 producing cell lines, and for producing large quantities of the virus, as well as a method and kit for detecting HHV-8 infection.
2. Description of the Background
Kaposi's sarcoma (KS) is a rare neoplasm of multi focal origin characterized by red-purple to blue-brown lesions of the skin. Cell proliferation occurs initially in the skin, eventually spreading to other body sites, in particular to the lower extremities. Lymphatic involvement is not unusual in KS patents, and may be present as a lymphadenopathy. Kaposi's sarcoma is the most frequent neoplastic manifestation of HIV infection, and is used as one of the criteria to decide whether an HIV-infected individual is defined as having Acquired Immunodeficiency Syndrome (AIDS).
Four different epidemiologic forms of KS have been described: sporadic or classic KS, endemic KS, KS encountered among transplant recipients receiving immunosuppresive therapies, and KS prevalent among patients with human immunodeficiency virus (HIV) infection. The "classic" form of KS was described over a century ago in predominantly elderly men of Mediterranean and Jewish descent. Men are affected by this form of KS 10 to 15 times more often than women, and those affected are typically in their 60s or older, and have an average survival time of approximately 10 years. The "endemic" form of KS has been recognized in certain geographic regions of Central Africa. This is a neoplasm which also affects men more frequently than women, is generally more aggressive than classic KS, and involves the lymph nodes and viscera, as well. A marked increase in the form of KS encountered in patients receiving immunosuppressive therapy, was mostly found in hepatic and renal transplant patients. AIDS patients have a probability of about 40% of developing cancer, especially Kaposi's sarcoma and/or non-Hodgkin's lymphoma. Kaposi's sarcoma has, additionally, been associated with lymphoid cancer in patients both with and without AIDS.
Epidemiologic studies conducted with classic KS, endemic KS, and transplant patients suggest that both the infectious agent and the immune status of the individual are of significance in acquiring KS. The unidentified infectious agent, presumably the causative agent, has been referred to as Kaposi sarcoma-associated herpes virus (KSHV) and human herpes virus-8 (HHV-8), interchangeably. Two novel DNA fragments were found in 90% of KS lesions associated with AIDS. The isolation and identification of these DNA fragments from the KS lesions of an AIDS patient, designated KS330 and KS631, suggested the involvement of an infectious agent. The base sequences of the two DNA fragments, and their flanking sequences were shown to have significant homology with two known herpes viruses: herpes virus saimiri and Epstein-Barr Virus (EBV). The latter two viruses belong to the gammaherpesvirinae subfamily, whose members have the ability to replicate in lymphoblastoid cells. Of all members of the subclass, EBV is the best studied. EBV has been shown to induce latent infection of peripheral blood lymphocytes in its natural host, and to immortalize lymphocytes in vitro, thereby causing the development of malignant lymphomas such as endemic Burkitt's lymphomas, AIDS-related non-Hodgkin's lymphomas and lymphoproliferative disorders which occur after transplantation. A subset of non-Hodgkin's lymphomas, referred to as body cavity-based lymphomas BCBLs, or primary effusion lymphomas (PELs), present unique clinical, morphologic, immunophenotypic, and molecular genetic characteristics. BCBLs, for instance, grow mainly in the pleural, pericardial, and abdominal cavities,
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Koeffler H. Phillip
Said Jonathan W.
Cedars-Sinai Medical Center
Salimi Ali
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