HIV-1 infection requires a functional integrase NLS

HIV-1 is able to infect nondividing cells productively in part because the postentry viral nucleoprotein complexes are actively imported into the nucl eus. In this manuscript, we identify a novel nuclear localization signal (N LS) in the viral integrase (IN) protein that is essential for virus replica tion in both dividing and nondividing cells. The IN NLS stimulates the effi cient nuclear accumulation of viral DNA as well as virion-derived IN protei n during the initial stages of infection but is dispensable for catalytic f unction. Because this NLS is required for infection irrespective of target cell proliferation, we suggest that interactions between uncoated viral nuc leoprotein complexes and the host cell nuclear import machinery are critica l for HIV-1 infection of all cells.