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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Farnet, C. M. Bushman, F. D. Wang, B. Lipford, J. R. |
| Description | Author Affiliation: Farnet CM ( Infectious Disease Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.); |
| Abstract | To replicate, HIV-1 must integrate a cDNA copy of the viral RNA genome into a chromosome of the host. The integration system is a promising target for antiretroviral agents, but to date no clinically useful integration inhibitors have been identified. Previous screens for integrase inhibitors have assayed inhibition of reactions containing HIV-1 integrase purified from an Escherichia coli expression system. Here we compare action of inhibitors in vitro on purified integrase and on subviral preintegration complexes (PICs) isolated from lymphoid cells infected with HIV-1. We find that many inhibitors active against purified integrase are inactive against PICs. Using PIC assays as a primary screen, we have identified three new anthraquinone inhibitors active against PICs and also against purified integrase. We propose that PIC assays are the closest in vitro match to integration in vivo and, as such, are particularly appropriate for identifying promising integration inhibitors. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 18 |
| Volume Number | 93 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1996-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antiviral Agents Pharmacology DNA Nucleotidyltransferases Antagonists & Inhibitors HIV-1 Physiology Virus Integration Drug Effects Virus Replication Anthraquinones DNA Metabolism DNA, Complementary Dideoxynucleotides Escherichia Coli Integrases Molecular Sequence Data RNA, Viral Thymine Nucleotides Topoisomerase I Inhibitors Zidovudine Analogs & Derivatives Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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