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.