The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection

Massimo Alfano, Nicolai Sidenius, Francesco Blasi, Guido Poli

Research output: Contribution to journalArticlepeer-review

Abstract

The binding of urokinase-type plasminogen activator (uPA) to its glycosyl-phosphatidylinositol (GPI) anchored receptor (uPAR) mediates a variety of functions in terms of vascular homeostasis, inflammation and tissue repair. Both uPA and uPAR, as well as their soluble forms detectable in plasma and other body fluids, represent markers of cancer development and metastasis, and they have been recently described as predictors of human immunodeficiency virus (HIV) disease progression, independent of CD4+ T cell counts and viremia. A direct link between the uPA/uPAR system and HIV infection was earlier proposed in terms of cleavage of gp120 envelope by uPA. More recently, a negative regulatory effect on both acutely and chronically infected cells has been linked to the noncatalytic portion of uPA, also referred to as the amino-terminal fragment (ATF). ATF has also been described as a major CD8 + T cell soluble HIV suppressor factor. In chronically infected promonocytic U1 cells this inhibitory effect is exerted at the very late stages of the virus life cycle, involving virion budding and entrapment in intracytoplasmic vacuoles, whereas its mechanism of action in acutely infected cells remains to be defined. Since uPAR is a GPI-anchored receptor it requires association with a signaling-transducing component and different partners, which include CD11b/CD18 integrin and a G-protein coupled receptor homologous to that for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalanine. Which signaling coreceptor(s) is(are) responsible for uPA-dependent anti-HIV effect remains currently undefined.

Original languageEnglish
Pages (from-to)750-756
Number of pages7
JournalJournal of Leukocyte Biology
Volume74
Issue number5
DOIs
Publication statusPublished - Nov 2003

Keywords

  • Interferon
  • Lymphocyte
  • Macrophage

ASJC Scopus subject areas

  • Cell Biology

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