John Libbey Eurotext



Recent progress in the biology and pharmacology of the HIV integrase Volume 6, issue 3, Mai - Juin 2002


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CNRS UMR8532, École normale supérieure, 61, avenue du Président-Wilson, 94235 Cachan Cedex

Integration of the HIV viral DNA into cellular DNA is performed by the viral integrase. This enzyme is obligatory for the efficient replication of the virus. The obtention of integrase inhibitors is therefore a major goal of anti-Aids research. The determination of two-domain structures has greatly increased our understanding of the nature of the active integrase oligomer, allowing the design of more relevant in vitro assays. Although the integrase activity still cannot be faithfully reproduced in vitro, active compounds were identified. Diketoacid derivatives identified as being active against the minimal oligomer in vitro manifested inhibition against physiological integrase in cells, thus crowing ten years of sustained effort. The pleiotropic integrase is also involved in the mechanisms of the translocation of the pre-integration complex. Moreover, the presence within this complex of factors involved in double-strand break repair shed a new light onto the cellular mechanism of retroviral integration.