The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.

Abstract

During HIV-1 infection, the viral capsid, which encloses the viral genome and accessory proteins required for reverse transcription (RT) and integration, traffics towards the nucleus and enters through the nuclear pore complex (NPC). Following entry into the nucleus, RT is completed and viral capsid disassembles releasing the preintegration complex (PIC) to integrate with the host chromosome. In this study, we investigated the early HIV-1 host factor CPSF6, and specifically focused on the C-terminal short amino acid nuclear localization signal (NLS) in CPSF6, in mediating viral nuclear entry and subsequent gene expression. Altering the NLS in CPSF6 with NLS from other proteins, significantly impacted HIV-1's ability to infect those cells. We further showed this defect in infection occurred at the level of viral integration. This study highlights the importance of the NLS in CPSF6 in dictating the NPC it associates with and its effect on HIV-1 infection. Moreover, our study emphasizes the function of NLS in targeting host cargos to different nuclear entry pathways.