澳大利亚新南威尔士大学D. A. Jacques团队近期取得重要工作进展，他们研究提出，HIV衣壳模拟FG核孔蛋白的核转运蛋白结合。相关研究成果2024年1月24日在线发表于《自然》杂志上。

据介绍，HIV可以感染不分裂的细胞，因为病毒衣壳可以克服核孔复合体的选择性屏障，将基因组直接输送到细胞核中。值得注意的是，完整的HIV衣壳比核孔扩散屏障规定的大小限制大1000多倍。核孔中心通道中的这种屏障由富含苯丙氨酸-甘氨酸（FG）二肽的内在无序的核通道蛋白结构域组成。通过多价FG相互作用，细胞核外蛋白及其结合物在该阶段溶解，以驱动核质转运。

通过对核孔复合体进行体外研究，研究人员发现HIV衣壳表面的口袋类似地与来自多个核孔蛋白的FG基序相互作用，这种相互作用使衣壳能够穿透FG核孔蛋白缩合物。这种核外蛋白模拟模型解决了HIV衣壳在核进入中作用的一个关键概念挑战，并解释了一个比任何已知细胞货物大得多的外源性实体如何能够无损地破坏核膜。

附：英文原文

Title: The HIV capsid mimics karyopherin engagement of FG-nucleoporins

Author: Dickson, C. F., Hertel, S., Tuckwell, A. J., Li, N., Ruan, J., Al-Izzi, S. C., Ariotti, N., Sierecki, E., Gambin, Y., Morris, R. G., Towers, G. J., Bcking, T., Jacques, D. A.

Issue&Volume: 2024-01-24

Abstract: HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine–glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.

DOI: 10.1038/s41586-023-06969-7

Source: https://www.nature.com/articles/s41586-023-06969-7