Amino-terminal fragment of urokinase-type plasminogen activator inhibits HIV-1 replication.
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.
Wada
M
M
Laboratories for Bioengineering and Research, JCR Pharmaceuticals Company, Ltd., 2-2-10 Murotani, Nishi-ku, Kobe, 651-2241, Japan. wada-m@jcrpharm.co.jp
Wada
N A
NA
Shirono
H
H
Taniguchi
K
K
Tsuchie
H
H
Koga
J
J
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015683:Gene Products, gag / Q000378:metabolism; D017930:Genes, Reporter / Q000187:drug effects / Q000235:genetics; D015488:HIV Antigens; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D012514:Sarcoma, Kaposi / Q000378:metabolism; D017741:Survivors; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology*; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects*; D054301:gag Gene Products, Human Immunodeficiency Virus
D017077:Culture Media, Conditioned; D015683:Gene Products, gag; D015488:HIV Antigens; C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D014568:Urokinase-Type Plasminogen Activator