Cutting edge: A short polypeptide domain of HIV-1-Tat protein mediates pathogenesis

HIV-1 encodes the transactivating protein Tat, which is essential for virus replication and progression of HIV disease. However, Tat has multiple doma ins, and consequently the molecular mechanisms by which it acts remain uncl ear. In this report, we provide evidence that cellular activation by Tat in volves a short core domain, Tat(21-40), containing only 20 aa including sev en cysteine residues highly conserved in most HIV-1 subtypes, Effective ind uction by Tat(21-40) of both NF-kappa B-mediated HIV replication and TAR-de pendent transactivation of HIV-long terminal repeat indicates that this sho rt sequence is sufficient to promote HIV infection, Moreover, Tat(21-40) po ssesses potent angiogenic activity, further underscoring its role in HIV pa thogenesis. These data provide the first demonstration that a 20-residue co re domain sequence of Tat is sufficient to transactivate, induce HIV replic ation, and trigger angiogenesis, This short peptide sequence provides a pot ential novel therapeutic target for disrupting the functions of Tat and inh ibiting progression of HIV disease.