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Title chromatin dynamics and HIV-1 nuclear trafficking.
Journal, issue, pagesbioRxiv, Year 2025
Publish dateDec 15, 2025
AuthorsZhen Hou / Yao Shen / Long Chen / Juan Shen / David I Stuart / Peijun Zhang /
PubMed AbstractThe organization and dynamics of chromatin within intact nuclei remain poorly defined, limiting understanding of how nuclear architecture influences macromolecular transport. HIV-1 provides a ...The organization and dynamics of chromatin within intact nuclei remain poorly defined, limiting understanding of how nuclear architecture influences macromolecular transport. HIV-1 provides a striking example of a large complex that must traverse this dynamic landscape to access integration sites within transcriptionally active regions. Here, we combine a functional nuclear import system with correlative cryo-electron tomography to visualize chromatin architecture and HIV-1 cores during nuclear penetration. Native nucleosomes resolved at 5.6 Å reveal four structural classes, from compact conformations at the nuclear periphery to open, flexible forms in the interior, defining a spatially heterogeneous and dynamic chromatin landscape. Within this environment, HIV-1 cores decorated with nuclear factors exclude nearby nucleosomes and preferentially associate with open chromatin. Disruption of CPSF6-capsid interactions abolishes these associations, confining viral cores to peripheral chromatin. These findings establish an framework linking chromatin structure and dynamics to HIV-1 nuclear trafficking and provide a structural basis for viral navigation within the dynamic nuclear landscape.
External linksbioRxiv / PubMed:41446222 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution5.6 - 20.0 Å
Structure data

EMDB-55441: In situ structure of wild-type HIV-1 CA hexamer prior to nuclear import
Method: EM (subtomogram averaging) / Resolution: 10.1 Å

EMDB-55443: In situ structure of wild-type HIV-1 CA hexamer post nuclear import
Method: EM (subtomogram averaging) / Resolution: 9.6 Å

EMDB-55445: In situ structure of N74D HIV-1 CA hexamer post nuclear import
Method: EM (subtomogram averaging) / Resolution: 12.8 Å

EMDB-55446: In situ structure of the H1-bound nucleosome
Method: EM (subtomogram averaging) / Resolution: 5.6 Å

EMDB-55447: In situ structure of stacking H1-bound nucleosomes
Method: EM (subtomogram averaging) / Resolution: 20.0 Å

EMDB-55448: In situ structure of the H1-bound nucleosome in stacking nucleosomes
Method: EM (subtomogram averaging) / Resolution: 9.9 Å

EMDB-55449: In situ structure of the core nucleosome
Method: EM (subtomogram averaging) / Resolution: 9.3 Å

EMDB-55450: In situ structure of the open-linker H1-bound nucleosome
Method: EM (subtomogram averaging) / Resolution: 12.1 Å

Source
  • Human immunodeficiency virus 1
  • Homo sapiens (human)

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