Furthermore, by targeting immune cells expressing RGD-binding integrin receptors via its RGD-binding site, extracellular Tat induces integrin-mediated signals and efficiently enters cells [14-16], resulting in the activation and modulation of several cellular functions in CD4+ T lymphocytes [6,7,17-22] and professional APCs [15,16], suggesting that Tat may play an important role in the chronic immune activation present during the HIV infection. Here, CD4 is linked to HIV infectious disease.