HIV-Tat dependent chemotaxis and invasion, key aspects of Tat mediated pathogenesis

Extracellular Tat acts as a pleiotropic molecule inducing several biologica l effects on different target cells. Tat stimulates the chemotaxis of numer ous cell types and it appears to have oncogenic activities, including actin g as a co-factor for Kaposi's sarcoma. The Tat protein has been shown to bi nd integrins through an RGD amino acid motif. Tat is an angiogenic factor a ble to induce the migration and invasion of endothelial and KS cells throug h the interaction of its basic domain with the VEGF receptor VEGFR2 (Flk-1/ KDR). We have also found that Tat is able to mimic chemokines, activating m onocyte migration through the `chemokine like' cysteine-core domain. Tat is a chemoattractant for dendritic cells, and both the RGD and basic domains appear to be involved in this response. In a recent study we demonstrated t hat Tat is chemotactic for PMN and induces Ca2+ mobilization in vitro. Expe riments using synthetic peptides showed that Tat activities on PMN are medi ated by the `chemokine like' region. Finally Tat is also able to induce B c ell chemotaxis, while its activity on helper T cells has not yet been clari fied. Here we review data on Tat-dependent chemotaxis and discuss the possi ble implications in Tat mediated pathogenesis.