Tat is synthesized during both the early and late stages of viral replication and is critical for these processes. The HIV-1 Tat protein is encoded by two exons and can be between 86 and 101 amino acids (aa) in length, depending on the specific viral strain. The Tat protein can be divided into six functional domains: (1) the N-terminal acidic aa region (aa 1-21), which has been linked to Tat immunosuppressive activity; (2) the cysteine-rich region (aa 22-37), which is responsible for transactivation of transcription; (3) the "core" region (aa 38-48), which is highly conserved; (4) the basic region (aa 49-57), which recognizes the transactivation response element (TAR) and plays important roles in both the nuclear localization of Tat and the entry of extracellular Tat into bystander cells[9]; (5) the glutamine-rich region (aa 60-72), which has the highest rate of sequence variation; and (6) the C-terminal region (aa 72-86 or 72-101). Furthermore, Tat is actively released from HIV-1-infected cells and acts as an extra-cellular toxin, which plays a crucial role in HIV-1 pathogenesis, including development of HIV-associated dementia, HIV-related opportunistic infections and Kaposi's sarcoma.