A cell line (Kaposi's sarcoma [KS] Y-1) established from a patient with KS is the first immortalized transformed cell line from KS, and is able to form lethal metastatic tumors of human origin in immunosuppressed mice. Human chorionic gonadotropin, a hormone expressed during pregnancy, blocks tumorigenesis and the growth of KS Y-1 and causes regression of established tumors in mice, apparently by inducing apoptosis. Apolipoprotein E has been effective in inhibiting the growth of KS-derived cell strains in culture and in murine KS models. Spindle cells resembling the putative tumor cell in KS have been found in primary peripheral mononuclear cell cultures. The frequency at which these cells are present appears to correlate with the risk for human immunodeficiency virus type 1-infected individuals to develop KS (i.e., homosexuals). One-half of the genome of human herspesvirus 7 (HHV-7) has been cloned, and the clones have been mapped by comparison with the genomes of HHV-6 and human cytomegalovirus. Total or partial sequence comparisons have been made with glycoproteins B, H and M; the major capsid protein; alkaline exonuclease; helicase; and phosphotransferase; and show that HHV-7 is most closely related to HHV-6 among all the human herpesviruses. Fragments of the KS-related HHV (KSHV/HHV-8) have been cloned and sequenced from African AIDS KS, endemic KS, Italian classic KS and B-cell lymphomas from U.S. AIDS patients. All are highly related to each other and to the published sequence. CD1+ cells selected from cultures of the human T-cell line SupT-1 have been exposed to human T-cell leukemia/lymphotropic virus I (HTLV-I), the etiologic agent of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), a multiple sclerosis-like disease. The exposed cells, but not the control cells, induce a fatal neurologic pathology when injected into immunodeficient mice. Media from the CD1+ cells also appear to induce the disease, although more slowly. These results suggest that a neurotoxic molecule is released by these cells, and that the situation may mimic that in HAM/TSP. This system may be useful in understanding the pathogenic mechanisms in this as well as similar human neurologic diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP007148-12
Application #
5201606
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code