HIV-1 INFECTION OF NONDIVIDING CELLS THROUGH THE RECOGNITION OF INTEGRASE BY THE IMPORTIN KARYOPHERIN PATHWAY/

The karyophilic properties of the HIV-1 nucleoprotein complex facilita te infection of nondividing cells such as macrophages and quiescent T lymphocytes, and allow the in vivo delivery of transgenes by HIV-deriv ed retroviral vectors into terminally differentiated cells such as neu rons. Although the viral matrix (MA) and Vpr proteins have previously been shown to play important roles in this process, we demonstrate her e that integrase, the enzyme responsible for mediating the integration of the viral genome in the host cell chromosome, can suffice to conne ct the HIV-1 preintegration complex with the cell nuclear import machi nery. This novel function of integrase reflects the recognition of an atypical bipartite nuclear localization signal by the importin/karyoph erin pathway.