Amino-terminal fragment of urokinase-type plasminogen activator inhibits HIV-1 replication

Biochem Biophys Res Commun. 2001 Jun 8;284(2):346-51. doi: 10.1006/bbrc.2001.4965.

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.

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Division / drug effects
  • Cells, Cultured
  • Clone Cells
  • Coculture Techniques
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Products, gag / metabolism
  • Genes, Reporter / drug effects
  • Genes, Reporter / genetics
  • HIV Antigens
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Long Terminal Repeat / genetics
  • HIV-1 / drug effects*
  • HIV-1 / growth & development
  • Humans
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Sarcoma, Kaposi / metabolism
  • Survivors
  • Transfection
  • Urokinase-Type Plasminogen Activator / chemistry
  • Urokinase-Type Plasminogen Activator / pharmacology*
  • Viral Proteins*
  • Virus Replication / drug effects*
  • gag Gene Products, Human Immunodeficiency Virus

Substances

  • Culture Media, Conditioned
  • Gene Products, gag
  • HIV Antigens
  • PLAUR protein, human
  • Peptide Fragments
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Viral Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1
  • Urokinase-Type Plasminogen Activator