Abstract
CD8+ T lymphocytes have been shown to produce unidentified soluble factors active in suppressing HIV-1 replication. In this study, we purified an HIV-1 suppressing activity from the culture supernatant of an immortalized CD8+ T cell clone, derived from an HIV-1 infected long-term nonprogressor, and identified this activity as the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA). ATF is catalytically inactive, but suppresses the release of viral particles from the HIV-1 infected cell lines via binding to its receptor CD87. In contrast, cell proliferation and the secretion of an HIV-1 LTR driven reporter gene product were not affected by ATF. These findings suggest that ATF may inhibit the assembly and budding of HIV-1, which provides a novel therapeutic strategy for AIDS.
Copyright 2001 Academic Press.
MeSH terms
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Division / drug effects
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Cells, Cultured
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Clone Cells
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Coculture Techniques
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Culture Media, Conditioned / chemistry
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Culture Media, Conditioned / pharmacology
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Dose-Response Relationship, Drug
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Gene Products, gag / metabolism
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Genes, Reporter / drug effects
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Genes, Reporter / genetics
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HIV Antigens
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HIV Infections / drug therapy*
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HIV Infections / metabolism
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HIV Long Terminal Repeat / genetics
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HIV-1 / drug effects*
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HIV-1 / growth & development
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Humans
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology*
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / metabolism
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Receptors, Urokinase Plasminogen Activator
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Sarcoma, Kaposi / metabolism
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Survivors
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Transfection
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Urokinase-Type Plasminogen Activator / chemistry
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Urokinase-Type Plasminogen Activator / pharmacology*
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Viral Proteins*
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Virus Replication / drug effects*
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gag Gene Products, Human Immunodeficiency Virus
Substances
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Culture Media, Conditioned
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Gene Products, gag
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HIV Antigens
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PLAUR protein, human
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Peptide Fragments
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Receptors, Cell Surface
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Receptors, Urokinase Plasminogen Activator
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Viral Proteins
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gag Gene Products, Human Immunodeficiency Virus
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p17 protein, Human Immunodeficiency Virus Type 1
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Urokinase-Type Plasminogen Activator