Important note: Information in this article was accurate in July 2000. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, July 26, 1999
Daniel J. DeNoon, Senior Editor
CW HENDERSON PUBLISHER -- An HIV-2-based gene therapy suppresses HIV-1. University of Michigan researchers Catherine M. Browning, David M. Markovitz, and colleagues have been developing a gene therapy approach to the treatment of AIDS. This approach targets the Tat activation-response (TAR) element of the AIDS virus by causing cells to express TAR decoys. They soak up the HIV protein Tat like a sponge, leaving less of it to bind to actual TAR and thus slowing a process essential to rapid HIV replication.
Now Browning et al. show that the HIV-2 TAR (TAR-2) actually binds HIV-1 Tat more efficiently than HIV-1 TAR (TAR-1).
"We have directly proven that TAR-2 can suppress HIV-1 replication and suggest that the HIV-2 decoy may prove useful for combating HIV-1 infection," they wrote.
"Our experiments show that the use of TAR-2, rather than TAR-1, as the RNA decoy for Tat and cellular cofactors may prove a significant advance in the design of gene therapy constructs for HIV."
Browning et al. reported their findings in the Journal of Virology ("Potent Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Gene Expression and Virus Production by an HIV-2 Tat Activation-Response RNA Decoy," J Virol 1999 Jun;73(6):5191-5).
The researchers suggested that the reason why TAR-2 is so much more effective than TAR-1 is that it has multiple sites for Tat interaction.
"The TAR-2 superstructure possesses three separate loop regions and may therefore more effectively compete with the single stem-loop structured TAR-1 for loop-binding cellular factors," they suggested.
Thus far Browning et al. have demonstrated TAR-2 efficacy in two different human cell lines. They are currently assessing the scope and duration of its anti-HIV effect and are exploring the combination of TAR-2 decoys with other gene therapies for AIDS.
This work was supported by grants from the National Institutes of Health and by fellowships from the Cellular Biotechnology Training Program and the Cancer Biology Training Program of the University of Michigan.
The corresponding author for this study is David M. Markovitz, 5220 MSRB III, University of Michigan Medical Center, 1150 W. Medical Center Dr., Ann Arbor, Michigan 48109-0640. Phone: (734) 764-1786. Fax: (734) 764-0101. Email: <dmarkov@umich.edu>.
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