REDUCED NUCLEAR IMPORT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PREINTEGRATION COMPLEXES IN THE PRESENCE OF A PROTOTYPIC NUCLEAR TARGETING SIGNAL

Nuclear import of the retroviral preintegration complex and integratio n of retroviral with host cell DNA are essential steps for completion of the virus life cycle. The preintegration complex of the lentivirus human immunodeficiency virus type 1 (HIV-1) displays karyophilic prope rties and, as a consequence, is rapidly directed to the host cell nucl eus by an energy-dependent transport pathway. The karyophilic properti es of nuclear proteins are governed by a nuclear localization sequence , the targeting function of which can be inhibited in the presence of excess targeting signals. Here we present evidence that the nuclear im port of a large karyophile-the preintegration complex of HIV-1-is inhi bited in the presence of a prototypic nuclear targeting signal of simi an virus 40 T antigen. This points to a novel strategy which prevents establishment of the provirus by interrupting nuclear localization of HIV-1 DNA.