Cone-shaped HIV-1 capsids are transported through intact nuclear pores.
Cone-shaped HIV-1 capsids are transported through intact nuclear pores.
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DOI：
10.1016/j.cell.2021.01.025
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发表时间：
2021-02-18
期刊：
影响因子：
64.5
通讯作者：
Beck M
中科院分区：
文献类型：
--
作者：
Zila V;Margiotta E;Turoňová B;Müller TG;Zimmerli CE;Mattei S;Allegretti M;Börner K;Rada J;Müller B;Lusic M;Kräusslich HG;Beck M
人体免疫机能丧失病毒（HIV-1）仍然是一个重大的健康威胁。病毒衣壳脱壳和病毒基因组的核输入对于生产性感染至关重要。HIV-1衣壳的大小通常被认为超过核孔复合物（NPC）的直径，表明衣壳脱壳必须在核输入之前发生。在这里，我们结合相关的光学和电子显微镜与subtomograms平均捕获的结构状态的逆转录活性HIV-1复合物在感染的T细胞。我们证明，直径的NPC在cellulo是足够的进口显然是完整的，锥形衣壳。随后的核输入，我们检测到破坏和空衣壳片段，表明通过打破衣壳开放，而不是通过拆卸成单独的亚基发生的复制复合物的脱壳。我们的数据直接可视化了HIV-1复制的关键步骤，并增强了我们对病毒生命周期的机械理解。HIV-1衣壳的核转位被3D CLEM/cryo-ET捕获T细胞中的核孔复合物充分扩张以容纳HIV-1衣壳锥形HIV-1衣壳通过核孔复合物转位在核内HIV-1衣壳破裂并释放其内部通过3D相关荧光和电子显微镜结合冷冻电子断层扫描可视化HIV-1衣壳的核转位，证明了受感染的T细胞中的核孔复合物被充分扩张，以允许锥形HIV-1衣壳通过。
Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid uncoating has to occur prior to nuclear import. Here, we combined correlative light and electron microscopy with subtomogram averaging to capture the structural status of reverse transcription-competent HIV-1 complexes in infected T cells. We demonstrated that the diameter of the NPC in cellulo is sufficient for the import of apparently intact, cone-shaped capsids. Subsequent to nuclear import, we detected disrupted and empty capsid fragments, indicating that uncoating of the replication complex occurs by breaking the capsid open, and not by disassembly into individual subunits. Our data directly visualize a key step in HIV-1 replication and enhance our mechanistic understanding of the viral life cycle. Nuclear translocation of HIV-1 capsids is captured by 3D CLEM/cryo-ET Nuclear pore complexes in T cells are sufficiently dilated to accommodate HIV-1 capsids Cone-shaped HIV-1 capsids translocate through nuclear pore complexes Inside the nucleus HIV-1 capsids rupture and release their interior Visualization of nuclear translocation of HIV-1 capsids by 3D correlative fluorescence light and electron microscope, combined with cryoelectron tomography, demonstrates that nuclear pore complexes in infected T cells are sufficiently dilated to allow cone-shaped HIV-1 capsids to pass through.
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DOI：
10.1038/nrmicro3503
发表时间：
2015-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Campbell EM;Hope TJ
通讯作者：
Hope TJ
影响因子：
7.7
作者：
Bejarano, David Alejandro;Peng, Ke;Kraeusslich, Hans-Georg
通讯作者：
Kraeusslich, Hans-Georg
DOI：
10.3390/v10110620
发表时间：
2018-11-10
期刊：
Viruses
影响因子：
--
作者：
Bejarano DA;Puertas MC;Börner K;Martinez-Picado J;Müller B;Kräusslich HG
通讯作者：
Kräusslich HG
影响因子：
5.4
作者：
ADACHI, A;GENDELMAN, HE;MARTIN, MA
通讯作者：
MARTIN, MA
影响因子：
48
作者：
Bindels, Daphne S.;Haarbosch, Lindsay;Gadella, Theodorus W. J., Jr.
通讯作者：
Gadella, Theodorus W. J., Jr.