![]() ![]() Once integrated, the provirus persists in the host cell and serves as a template for the transcription of viral genes and replication of the viral genome, leading to the production of new viruses. The genomic RNA of the virus is used to produce a copy of viral DNA by reverse transcription, and the last of these enzymes, integrase, catalyses the covalent insertion of this DNA into the chromosomes of the infected cells. Viral replication is driven by a molecular motor consisting of the three viral enzymes: the reverse transcriptase, protease and integrase (IN). AIDS morbidity and mortality have led to efforts to identify effective inhibitors of the replication of this virus. The human immunodeficiency virus is the causal agent of AIDS. 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. Moreover, recent studies demonstrated the existence of a weak palindromic consensus found at the integration sites. 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. 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). 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. The process of integration can be divided into two sequential reactions. Integrase, a retroviral enzyme, catalyses integration. Integration of retroviral DNA is an obligatory step of retrovirus replication because proviral DNA is the template for productive infection.
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