德国欧洲分子生物学实验室Martin Beck、海德堡大学Hans-Georg Kräusslich等研究人员合作发现，圆锥形的HIV-1衣壳能够通过完整的核孔来运输。该研究于2021年2月18日发表于国际一流学术期刊《细胞》。

研究人员表示，人类免疫缺陷病毒（HIV-1）仍然是主要的健康威胁。病毒衣壳的脱壳和病毒基因组的核导入对于复制性感染至关重要。一般认为，HIV-1衣壳的大小超过了核孔复合体（NPC）的直径，从而表明衣壳必须在核输入之前进行脱壳。

研究人员结合光学-电子相关显微镜与子断层扫描图平均化来捕获感染的T细胞中具有逆转录能力的HIV-1复合物结构状态。研究人员证明细胞中NPC的直径足以输入看似完整的圆锥形衣壳。核导入后，研究人员检测到了被破坏的空衣壳片段，这表明复制复合物的脱壳是通过打开衣壳而不是分解成单个亚基而发生的。这些数据直接显示了HIV-1复制的关键步骤，并增强了人们对病毒生命周期的机制理解。

附：英文原文

Title: Cone-shaped HIV-1 capsids are transported through intact nuclear pores

Author: Vojtech Zila, Erica Margiotta, Beata Turoňová, Thorsten G. Müller, Christian E. Zimmerli, Simone Mattei, Matteo Allegretti, Kathleen Brner, Jona Rada, Barbara Müller, Marina Lusic, Hans-Georg Krusslich, Martin Beck

Issue&Volume: 2021/02/18

Abstract: 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.

DOI: 10.1016/j.cell.2021.01.025

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00068-4