EQUIVALENT INHIBITION OF HALF-SITE AND FULL-SITE RETROVIRAL STRAND TRANSFER-REACTIONS BY STRUCTURALLY DIVERSE COMPOUNDS

In vitro assay systems which use recombinant retroviral integrase (IN) and short DNA oligonucleotides fail to recapitulate the full-site int egration reaction as it is known to occur in vivo. The relevance of us ing such circumscribed in vitro assays to define inhibitors of retrovi ral integration has not been formerly demonstrated. Therefore, we anal yzed a series of structurally diverse inhibitors with respect to inhib ition of both half-site and full-site strand transfer reactions with e ither recombinant or virion-produced IN. Half-site and full-site react ions catalyzed by avian myeloblastosis virus and human immunodeficienc y virus type 1 (HIV-1) IN from virions are shown to be equivalently se nsitive to inhibition by compounds which inhibit half-site reactions c atalyzed by the recombinant HIV-1 IN. These studies therefore support the utility of using in vitro assays employing either recombinant or v irion-derived IN to identify inhibitors of integration.