2025-01-17 マックス・プランク研究所
<関連情報>
- https://www.mpg.de/24023380/hivcapsid-cracks-the-npc?c=2249
- https://www.cell.com/cell/fulltext/S0092-8674(24)01421-1
HIVカプシドの核膜孔通過 Passage of the HIV capsid cracks the nuclear pore
Jan Philipp Kreysing∙ Maziar Heidari∙ Vojtech Zila∙ … ∙ Gerhard Hummer∙ Hans-Georg Kräusslich∙ Martin Beck
Cell Published:January 17, 2025
DOI:https://doi.org/10.1016/j.cell.2024.12.008
Graphical abstract
Highlights
•Cone-shaped HIV-1 capsids accumulate at and pass through nuclear pores in macrophages
•The capsid lattice remains largely intact during nuclear entry
•Nuclear pores can crack open upon passage of the HIV-1 capsid
•Nuclear pore cracking may relieve steric blockage of HIV-1 capsid
Summary
Upon infection, human immunodeficiency virus type 1 (HIV-1) releases its cone-shaped capsid into the cytoplasm of infected T cells and macrophages. The capsid enters the nuclear pore complex (NPC), driven by interactions with numerous phenylalanine-glycine (FG)-repeat nucleoporins (FG-Nups). Whether NPCs structurally adapt to capsid passage and whether capsids are modified during passage remains unknown, however. Here, we combined super-resolution and correlative microscopy with cryoelectron tomography and molecular simulations to study the nuclear entry of HIV-1 capsids in primary human macrophages. Our data indicate that cytosolically bound cyclophilin A is stripped off capsids entering the NPC, and the capsid hexagonal lattice remains largely intact inside and beyond the central channel. Strikingly, the NPC scaffold rings frequently crack during capsid passage, consistent with computer simulations indicating the need for NPC widening. The unique cone shape of the HIV-1 capsid facilitates its entry into NPCs and helps to crack their rings.
