MOLECULAR MECHANISM OF RETROVIRAL DNA INTEGRATION

The integration of retroviral DNA appears to be obligatory for the eff icient replication of retroviruses in their respective host cells. Dur ing a natural infection, integration takes place in a process that inc ludes biochemically and temporally discrete steps. These are: (1) the removal of two nucleotides from the 3' ends of newly synthesized linea r viral DNA in the host cell cytoplasm; (2) transport of the trimmed v iral DNA to the nucleus within a viral protein/DNA complex; and (3) in sertion of the viral DNA into host cell DNA via a concerted cleavage a nd ligation reaction. The cleavage of viral DNA and its subsequent joi ning to host DNA are catalyzed by the retroviral enzyme, integrase (IN ). Elucidation of the mechanistic details of these catalytic activitie s of IN has relied heavily upon the use of relatively simple in vitro assays which recapitulate the in vivo reactions. These assays and the information derived from them should also facilitate the search for po tential inhibitors of IN with the ultimate goal of providing a means t o halt retroviral infections, such as that which causes the acquired i mmunodeficiency syndrome (AIDS), effectively.