Viral replication

Virology

Chemistry

Capsid

Cell nucleus

Infectivity

Polyadenylation

Nuclear pore

Nuclear transport

Virus

Biology

Gene

Cytoplasm

Nuclear export signal

Cleavage and polyadenylation specificity factor

Cell biology

Gene expression

Nuclear protein

Transcription factor

Human immunodeficiency virus (HIV)

Genetics

eLife

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.

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