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 integration 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 properties and, as a consequence, is rapidly directed to the host cell nucleus by an energy-dependent transport pathway. The karyophilic properties 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 import of a large karyophile-the preintegration complex of HIV-1-is inhibited in the presence of a prototypic nuclear targeting signal of simian virus 40 T antigen. This points to a novel strategy which prevents establishment of the provirus by interrupting nuclear localization of HIV-1 DNA. Permissiveness of the host cell to productive infection by most oncoretroviruses is cell cycle dependent (26). Thus, in nondividing cells, virus replication is arrested at a stage between retroviral DNA synthesis and integration of viral with host cell DNA (21). In contrast, establishment of the inte-grated provirus following infection by lentiviruses, such a