VIB Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium; Department of Biochemistry and Microbiology, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
VIB Center for Medical Biotechnology, VIB, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium; Department of Biomolecular Medicine, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium.
Cell Host Microbe. 2024 Oct 9;32(10):1705-1724.e14. doi: 10.1016/j.chom.2024.09.002.
Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1.
人溶瘤病毒抗性蛋白 2（MX2）可通过一种需要 MX2 与病毒衣壳相互作用的过程，在进入后阶段限制 HIV-1 和疱疹病毒。然而，其他宿主细胞因子的参与仍知之甚少。在这里，我们绘制了 MX2 的临近互作组图谱，发现富含与核孔复合物相关的苯丙氨酸-甘氨酸（FG）丰富蛋白以及细胞质核糖核蛋白颗粒的一部分的蛋白强烈富集。MX2 与这些蛋白相互作用，形成多蛋白细胞质生物分子凝聚物，这对于其抗 HIV-1 和抗单纯疱疹病毒 1（HSV-1）活性是必需的。MX2 凝聚物的形成需要无规的 N 端区域和 MX2 二聚化。进入的 HIV-1 和 HSV-1 衣壳与这些动态细胞质生物分子凝聚物中的 MX2 结合，阻止其病毒基因组进入细胞核。因此，MX2 形成细胞质凝聚物，可能作为核孔诱饵，捕获衣壳并诱导过早释放病毒基因组，从而干扰 HIV-1 和 HSV-1 的核靶向。
