HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex
HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex
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DOI：
10.7554/elife.41800
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发表时间：
2019-01-23
期刊：
影响因子：
7.7
通讯作者：
Kraeusslich, Hans-Georg
中科院分区：
文献类型：
--
作者：
Bejarano, David Alejandro;Peng, Ke;Kraeusslich, Hans-Georg
HIV-1复制复合物通过完整的核孔复合物进入核对于成功感染至关重要。宿主蛋白裂解和多聚腺苷酸化特异性因子6（CPSF 6）与早期HIV-1复制的不同阶段有关。应用HIV-1逆转录和前整合复合物（RTC/PIC）的定量显微镜，我们发现CPSF 6被强烈招募到核复制复合物中，但在原代人巨噬细胞中不存在胞质RTC/PIC。CPSF 6的消耗或缺乏CPSF 6结合导致HIV-1亚病毒复合物在巨噬细胞核膜处的积累和感染性降低。双色受激发射损耗显微镜检查表明，在这些情况下，HIV-1复合物保留在核孔内，并在核篮附近进行CA-多聚体依赖性CPSF 6聚类。我们建议，在巨噬细胞中的HIV-1亚病毒复合物的核进入介导的Nup 153和CPSF 6的六聚体CA晶格的连续结合。
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.