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IFN- Induces Endothelial Cells to Proliferate and to Invade the Extracellular Matrix in Response to the HIV-1 Tat Protein: Implications for AIDS-Kaposi’s Sarcoma Pathogenesis¹

Valeria Fiorelli^*, Giovanni Barillari, Elena Toschi, Cecilia Sgadari, Paolo Monini, Michael Stürzl and Barbara Ensoli^2,

^* Department of Allergy and Clinical Immunology, University of Rome "La Sapienza," Rome, Italy; Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy; and Gesellschaft für Strahlung und Umweltforschung (GSF)-National Research Center for Environment and Health, Institute of Molecular Virology, Neuherberg and Technical University of Munich, Institute of Virology, Munich, Germany

Previous studies indicated that the Tat protein of HIV functions as a progression factor in Kaposi’s sarcoma (KS), an angioproliferative disease common and aggressive in HIV-1-infected individuals (AIDS-KS). In particular, Tat that is released by infected cells stimulates the growth and invasion of spindle cells of endothelial origin derived from KS lesions (KS cells). Other work suggested that inflammatory cytokines may act as initiating factors in KS since they induce normal endothelial cells to acquire the same phenotype and functional features of KS cells, including the responsiveness to Tat. In this study, we show that among the inflammatory cytokines increased in AIDS-KS lesions, IFN- alone is sufficient to induce endothelial cells to proliferate and to invade the extracellular matrix in response to Tat. This is because IFN- up-regulates the expression and activity of the receptors for Tat identified as the integrins ₅ß₁ and _vß₃. These results suggest that, by triggering Tat effects, IFN- plays a major role in AIDS-KS pathogenesis.

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