英国伦敦大学学院Clare Jolly课题组探明了HIV-1信号重塑核孔以允许感染。2026年5月6日出版的《自然》杂志发表了这项成果。

在这里，研究人员解决了这个问题，并表明HIV-1在核孔复合体（NPC）的衣壳核输入是静息T细胞感染的瓶颈，但HIV-1通过在细胞-细胞扩散过程中触发受体介导的信号传导来驱动核输入和许可感染，从而克服了这一瓶颈。将病毒和细胞分析与超分辨率成像相结合，课题组人员发现HIV-1感染和未感染的T细胞之间的接触触发CD4-LCK信号，激活CDK1，独立于细胞周期进入，磷酸化核孔蛋白并启动NPC以促进HIV-1核输入。

关键的是，细胞间接触也加速了活化T细胞的核输入，这为为什么细胞-细胞扩散主导感染提供了一个范例。相比之下，HIV-1病毒粒子不会触发这种反应，这就解释了为什么静止的T细胞不能被无细胞病毒有效地感染。课题组提出HIV-1已经进化到在细胞-细胞扩散过程中选择性激活CD4信号以调节NPC步骤中的感染，这为静止T细胞如何在体内感染提供了解释。

研究人员表示，HIV-1很容易在体内静息CD4⁺ T细胞中检测到。然而，静息T细胞在体外对无细胞病毒感染具有高度的耐受性，并且需要有丝分裂激活才能变得允许。这个悖论提出了一个基本问题：是什么让T细胞允许HIV-1的存在。

附：英文原文

Title: HIV-1 signalling remodels nuclear pores to licence infection

Author: Mesner, Dejan, Whelan, Matthew V. X., Shivkumar, Maitreyi, Reuschl, Ann-Kathrin, Chiozzi, Riccardo Zenezini, Thalassinos, Konstantinos, de Bruin, Robertus A. M., Jolly, Clare

Issue&Volume: 2026-05-06

Abstract: HIV-1 is readily detected in resting CD4+ T cells in vivo1,2,3,4. However, resting T cells are highly refractory to cell-free virus infection in vitro5,6,7 and require mitogenic activation to become permissive. This paradox raises the fundamental question of what makes a T cell permissive for HIV-1. Here we address this and show that HIV-1 capsid nuclear import at the nuclear pore complex (NPC) is a bottleneck to resting T cell infection, but that HIV-1 overcomes this by triggering receptor-mediated signalling during cell–cell spread to drive nuclear import and licence infection. Coupling viral and cellular assays with super-resolution imaging, we show that contact between HIV-1 infected and uninfected T cells triggers CD4–LCK signalling that activates CDK1, independent of cell-cycle entry, phosphorylating nucleoporins and priming the NPC to promote HIV-1 nuclear import. Critically, cell–cell contact also accelerates nuclear import in activated T cells, providing a paradigm for why cell–cell spread dominates infection. By contrast, HIV-1 virions do not trigger this response, explaining why resting T cells cannot be efficiently infected by cell-free virus. We propose that HIV-1 has evolved to selectively activate CD4 signalling during cell–cell spread to regulate infection at the step of the NPC, offering an explanation for how resting T cells can be infected in vivo.

DOI: 10.1038/s41586-026-10453-3

Source: https://www.nature.com/articles/s41586-026-10453-3