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CUTTING EDGE |
*
Laboratory of Parasitic Biology and Biochemistry and
Immunopathogenesis Section, Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
§
Immunopathology Section and
¶
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892
HIV-1 encodes the transactivating protein Tat, which is
essential for virus replication and progression of HIV disease.
However, Tat has multiple domains, and consequently the molecular
mechanisms by which it acts remain unclear. In this report, we provide
evidence that cellular activation by Tat involves a short core domain,
Tat21–40, containing only 20 aa including seven cysteine
residues highly conserved in most HIV-1 subtypes. Effective induction
by Tat21–40 of both NF-
B-mediated HIV replication and
TAR-dependent transactivation of HIV-long terminal repeat indicates
that this short sequence is sufficient to promote HIV infection.
Moreover, Tat21–40 possesses potent angiogenic activity,
further underscoring its role in HIV pathogenesis. These data provide
the first demonstration that a 20-residue core domain sequence of Tat
is sufficient to transactivate, induce HIV replication, and trigger
angiogenesis. This short peptide sequence provides a potential novel
therapeutic target for disrupting the functions of Tat and inhibiting
progression of HIV disease.
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