6-OXOCYTIDINE CONTAINING OLIGONUCLEOTIDES INHIBIT THE HIV-1 INTEGRASE IN VITRO

Abstract

Integration of the proviral DNA into the genome of infected cells is a key step of HIV-1 replication. Integration is catalyzed by the viral enzyme integrase (IN). 6-oxocytidine-containing oligonucleotides were found to be efficient inhibitors of integrase in vitro. The inhibitory effect is sequence-specific and strictly requires the presence of the 6-oxocytidine base. It is due to the impairment of the integrase binding to its substrate and does not involve an auto-structure of the oligonucleotide.

ACKNOWLEDGMENTS

This work was supported by funds from INTAS grant No. 96-1216, from the Agence Nationale de Recherche sur le Sida (ANRS) and SIDACTION. P.B. gratefully acknowledges fellowship support from SIDACTION.