HIV-1 INFECTION INDUCES FUNCTIONAL ALTERATIONS IN HUMAN LIVER ENDOTHELIAL-CELLS IN PRIMARY CULTURE

Objectives: Since human liver endothelial cells allow HIV-1 multiplica tion in vitro, we investigated whether HIV induced functional alterati ons in these cells in primary culture. Design: Direct evidence of the replication of HIV in endothelial cells is sparse, but clotting abnorm alities and thrombi, which suggest the existence of an endothelial dys function, have been observed in HIV-infected patients. We therefore st udied the storage and release of endothelial-specific factors in prima ry cultures of liver endothelial cells infected with HIV, as well as t heir cytoskeleton, pinocytic and phagocytic properties. Methods: Intra cellular storage of von Willebrand's factor (vWF) was determined by im munofluorescence and computer image analysis. Excretion of vWF, protei n S and endothelin-1 was measured using an enzyme-linked immunosorbent assay and radioimmunoassay. Cytoskeletal constituents were studied by light microscopy. The pinocytosis of acetylated low-density lipoprote ins and the phagocytosis of latex beads were analysed under light and electron microscopy. Results: The synthesis of vWF is markedly decreas ed in HlV-infected liver endothelial cells, as is the excretion of end othelin-1. In contrast, the excretion of protein S remains unaffected and the cytoskeletal network appears to be unaltered. Pinocytosis and phagocytosis are preserved. Conclusions: HIV infection triggers non-le thal functional alterations in cultured human liver sinusoidal endothe lial cells, with a selective impairment in the storage and/or the excr etion of endothelial-specific factors such as vWF. This functional mod ulation could play a role in the pathophysiology of HIV-induced diseas e.