HIV/AIDS Drug Development: HIV-1 replication inhibited by artificial transcription factors targeting primer binding site

AIDSWEEKLY Plus; Monday, May 22, 2006
Staff Medical Writers

According to recent research from the United States, "The human immunodeficiency virus type 1 (HIV-1) primer-binding site (PBS) is a highly conserved region in the HIV genome and represents an attractive target for the development of new anti-HIV therapies.

"In this study, we designed four artificial zinc finger transcription factors to bind at or adjacent to the PBS and repress transcription from the HIV-1 long terminal repeat (LTR). These proteins bound to the LTR in vivo, as demonstrated by the chromatin immunoprecipitation assay."

"In transient reporter assays, three of the four proteins repressed transcription of a reporter driven by the HIV-1 LTR. Only one of these proteins, however, designated KRAB-PBS2, was able to prevent virus production when transduced into primary lymphocytes.

"We observed >90% inhibition of viral replication over the course of several weeks compared to untransduced cells, and no significant cytotoxicity was observed," wrote S.R. Eberhardy and colleagues at Scripps Research Institute.

"Long-term exposure of HIV-1 to KRAB-PBS2 induced mutations in the HIV-1 PBS that reduced the effectiveness of the repressor," continued scientists, "but these mutations also resulted in decreased rates of viral replication."

The authors concluded, "These results show that KRAB-PBS2 has the potential to be used in antiviral therapy for AIDS patients and might complement other gene-based strategies."

Eberhardy and colleagues published their study in the Journal of Virology (Inhibition of human immunodeficiency virus type 1 replication with artificial transcription factors targeting the highly conserved primer-binding site. J Virol. 2006 Mar;80(6):2873-83).

For additional information, contact C.F. Barbas, Scripps Research Institute, Dept. Molecular Biology, BCC 550, 10050 N Torrey Pines Rd., La Jolla, CA 92037, USA.

Publisher contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: La Jolla, California, United States, HIV/AIDS, Pharmaceutical & Drug Development, Artificial Transcription Factor, Viral Inhibition, Primer Binding Site.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Eberhardy SR, Goncalves J, Coelho S, et al., "Inhibition of human immunodeficiency virus type 1 replication with artificial transcription factors targeting the highly conserved primer-binding site", J Virol. 2006 Mar;80(6):2873-83.

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