HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex

• Main Authors: David Alejandro Bejarano, Ke Peng, Vibor Laketa, Kathleen Börner, K Laurence Jost, Bojana Lucic, Bärbel Glass, Marina Lusic, Barbara Müller, Hans-Georg Kräusslich
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-01-01
• Series: eLife
• Subjects: Human immunodeficiency virus; CPSF6; macrophages; pre-integration complex; nuclear pore complex; nuclear import
• Online Access: https://elifesciences.org/articles/41800

Nuclear entry of HIV-1 replication complexes through intact nuclear pore complexes is critical for successful infection. The host protein cleavage-and-polyadenylation-specificity-factor-6 (CPSF6) has been implicated in different stages of early HIV-1 replication. Applying quantitative microscopy of HIV-1 reverse-transcription and pre-integration-complexes (RTC/PIC), we show that CPSF6 is strongly recruited to nuclear replication complexes but absent from cytoplasmic RTC/PIC in primary human macrophages. Depletion of CPSF6 or lack of CPSF6 binding led to accumulation of HIV-1 subviral complexes at the nuclear envelope of macrophages and reduced infectivity. Two-color stimulated-emission-depletion microscopy indicated that under these circumstances HIV-1 complexes are retained inside the nuclear pore and undergo CA-multimer dependent CPSF6 clustering adjacent to the nuclear basket. We propose that nuclear entry of HIV-1 subviral complexes in macrophages is mediated by consecutive binding of Nup153 and CPSF6 to the hexameric CA lattice.