TY  - INPR
A1  - Kreysing, Jan Philipp
A1  - Heidari, Maziar
A1  - Zila, Vojtech
A1  - Cruz León, Sergio
A1  - Obarska-Kosinska, Agnieszka
A1  - Laketa, Vibor
A1  - Welsch, Sonja
A1  - Köfinger, Jürgen
A1  - Turoňová, Beata
A1  - Hummer, Gerhard
A1  - Kräusslich, Hans-Georg
A1  - Beck, Martin
T1  - Passage of the HIV capsid cracks the nuclear pore
T2  - bioRxiv
N2  - Upon infection, human immunodeficiency virus (HIV-1) releases its cone-shaped capsid into the cytoplasm of infected T-cells and macrophages. As its largest known cargo, the capsid enters the nuclear pore complex (NPC), driven by interactions with numerous 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 cryo electron tomography and molecular simulations to study nuclear entry of HIV-1 capsids in primary human macrophages. We found 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.
Y1  - 2024
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/84462
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-844621
UR  - https://www.biorxiv.org/content/10.1101/2024.04.23.590733v1
IS  - 2024.04.23.590733 Version 1
PB  - bioRxiv
ER  -