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| Title | HIV-1 nuclear import is selective and depends on both capsid elasticity and nuclear pore adaptability. |
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| Journal, issue, pages | Nat Microbiol, Vol. 10, Issue 8, Page 1868-1885, Year 2025 |
| Publish date | Jul 7, 2025 |
 Authors | Zhen Hou / Yao Shen / Stanley Fronik / Juan Shen / Jiong Shi / Jialu Xu / Long Chen / Nathan Hardenbrook / Alan N Engelman / Christopher Aiken / Peijun Zhang /    |
| PubMed Abstract | Lentiviruses, such as HIV-1, infect non-dividing cells by traversing the nuclear pore complex (NPC); however, the detailed molecular processes remain unclear. Here we reconstituted functional HIV-1 ...Lentiviruses, such as HIV-1, infect non-dividing cells by traversing the nuclear pore complex (NPC); however, the detailed molecular processes remain unclear. Here we reconstituted functional HIV-1 nuclear import using permeabilized T cells and isolated HIV-1 cores, which significantly increases import events, and developed an integrated three-dimensional cryo-correlative workflow to specifically target and image 1,489 native HIV-1 cores at 4 distinct nuclear import stages using cryo-electron tomography. We found HIV-1 nuclear import depends on both capsid elasticity and nuclear pore adaptability. The NPC acts as a selective filter, preferentially importing smaller cores, while expanding and deforming to accommodate their passage. Brittle mutant cores fail to enter the NPC, while CPSF6-binding-deficient cores enter but stall within the NPC, leading to impaired nuclear import. This study uncovers the interplay between the HIV-1 core and the NPC and provides a framework to dissect HIV-1 nuclear import and downstream events, such as uncoating and integration. |
 External links | Nat Microbiol / PubMed:40624219 / PubMed Central |
| Methods | EM (subtomogram averaging) |
| Resolution | 11.05 - 36.5 Å |
| Structure data |  EMDB-52887: In-situ structure of HIV-1 CA hexamer in NPC  EMDB-52888: In-situ structure of HIV-1 CA hexamer before the nuclear import  EMDB-52889: In-situ structure of HIV-1 CA hexamer after the nuclear import  EMDB-53083: Cytoplasmic ring structure of the NPC of CEM cells  EMDB-53084: Inner ring structure of the NPC of CEM cells  EMDB-53085: Luminal ring structure of the NPC of CEM cells  EMDB-53086: Nuclear ring structure of the NPC of CEM cells |
| Source |
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HIV-1 (virus)
Homo sapiens (human)