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 domains, and consequently the molecular mechanisms by which it acts remain unclear. In this report, we provide evidence that cellular activation by Tat in...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-07, Vol.163 (1), p.15-20
Main Authors: Boykins, R A, Mahieux, R, Shankavaram, U T, Gho, Yong Song, Lee, S F, Hewlett, I K, Wahl, L M, Kleinman, H K, Brady, J N, Yamada, K M, Dhawan, S
Format: Article
Language:English
Subjects:
Human immunodeficiency virus 1
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Summary: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, Tat sub(21-40), containing only 20 aa including seven cysteine residues highly conserved in most HIV-1 subtypes. Effective induction by Tat sub(21-40) of both NF- Kappa 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, Tat sub(21-40) 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.
ISSN:0022-1767