Integrase and integration: biochemical activities of HIV-1 integrase.
Integration of retroviral DNA is an obligatory step of retrovirus replication because proviral DNA is the template for productive infection. Integrase, a retroviral enzyme, catalyses integration. The process of integration can be divided into two sequential reactions. The first one, named 3'-processing, corresponds to a specific endonucleolytic reaction which prepares the viral DNA extremities to be competent for the subsequent covalent insertion, named strand transfer, into the host cell genome by a trans-esterification reaction. Recently, a novel specific activity of the full length integrase was reported, in vitro, by our group for two retroviral integrases (HIV-1 and PFV-1). This activity of internal cleavage occurs at a specific palindromic sequence mimicking the LTR-LTR junction described into the 2-LTR circles which are peculiar viral DNA forms found during viral infection. Moreover, recent studies demonstrated the existence of a weak palindromic consensus found at the integration sites. Taken together, these data underline the propensity of retroviral integrases for binding symmetrical sequences and give perspectives for targeting specific sequences used for gene therapy.
Delelis
Olivier
O
LBPA, CNRS, Ecole Normale Supérieure de Cachan, 61 Avenue du Président Wilson, 94235 Cachan, France. delelis@lbpa.ens-cachan.fr
Carayon
Kevin
K
Saïb
Ali
A
Deprez
Eric
E
Mouscadet
Jean-François
JF
D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology*; D016662:Virus Integration
D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1