The uPA/uPAR System and suPAR in HIV Infection

The urokinase Plasminogen Activator Receptor (uPAR) is linked to the surface of immune cells and involved in multiple immune functions including cell adhesion, chemotaxis, migration, angiogenesis, fibrinolysis, proliferation, differentiation and signal transduction. uPAR binds and activates urokinase resulting in extracellular matrix degradation and remodeling. Also, uPAR can bind the extracellular matrix protein vitronectin promoting cell adhesion and migration.

uPAR can be cleaved from the cell surface resulting in soluble uPAR (suPAR). suPAR levels are increased by various infectious diseases associated with systemic inflammation such as HIV infection. Several studies have shown that those with the highest suPAR levels have increased disease progression and high risk of mortality.

Furthermore, uPA was demonstrated to exert antiretroviral activity by inhibiting late steps in HIV replication cycle in various cell lines, through mechanisms dependent on cell adhesion. Future research will determine whether the emerging role of the uPA/uPAR/suPAR-system in HIV infection can be implemented in HIV drug development and in the use of suPAR measurements for initiating antiretroviral therapy and for monitoring treatment efficacy.