7th Conference - S1/title> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <meta name="Date" content="12.29.1998"> <meta name="Author" content="Mike Kouroupis"> <meta http-equiv="Reply-to" content="MikeK60@Yahoo.com"> <meta name="GENERATOR" content="Dreamweaver 1.2"> <meta name="description" content="S1 <b><i>HIV</i> cDNA Integration: Mechanism and Design of Inhibitors</b>. F. D. BUSHMAN*. The Salk Inst. for Biological Studies, La Jolla, CA."> </head> <body bgcolor="#F7F7E7" topmargin="0" leftmargin="0" marginwidth="0" marginheight="0" link="#00639c" vlink="#660066" alink="#000066"> <table width="100%" border="0" cellpadding="0" cellspacing="0" bgcolor="#FF9C31"> <tr> <td colspan="3"><img src="../images/title_txt_no_home.gif" width="760" height="32" alt="7th Conference on Retroviruses and Opportunistic Infections"></td> </tr> </table> <table width="80%" border="0" cellpadding="0" cellspacing="0"> <tr> <td width="20%" align="left" valign="top"> </td> <td width="80%" align="left" valign="top"> <p><br> S1 <b><i>HIV</i> cDNA Integration: Mechanism and Design of Inhibitors</b>. F. D. BUSHMAN*. The Salk Inst. for Biological Studies, La Jolla, CA. Retroviruses are distinguished from other viruses by two steps in the viral life cycle: 1) reverse transcription, which results in the production of a double stranded cDNA copy of the viral RNA genome, and 2) integration, which results in the covalent connection of that cDNA to host DNA. Studies of the HIV integration system are particularly topical, since the HIV-encoded integrase protein is at present the only viral enzyme for which clinically useful inhibitors are not available. Our studies focus on the mechanism of integration, with the goal of developing understanding of the mechanism and aiding the design of inhibitors. Integration activity for studies in vitro can be obtained from integrase protein over expressed in bacteria, or from replication intermediates in HIV-infected cells ("preintegration complexes" or PICs). We are presently working to characterize PICs from infected cells and assemble such complexes from purified components. Our picture of the protein-DNA complexes involved has been enriched by the determination of a new high resolution X-ray structure of two out of three of the protein domains. Further studies center on understanding and controlling target site selection, and the design of new small molecule inhibitors active against integrase. Particularly exciting are new findings of integrase inhibitors active against HIV in cell culture. </p> </td> </tr> </table> <table width="80%" border="0" cellpadding="0" cellspacing="0"> <tr> <td width="20%"> </td> <td width="80%"> <hr width="100%">  <p align="center"><font face="Arial, Helvetica, sans-serif" size="1">© 7th Conference on Retroviruses and Opportunistic Infections,<br> Foundation for Retrovirology and Human Health</font></p> </td> </tr> </table> <p> </p> </body> </html>