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bioRxiv · 10.64898/2025.12.12.693995

In situ chromatin dynamics and HIV-1 nuclear trafficking

Hou, Z.·Shen, Y.·Shen, J.·Stuart, D. I.·zhang, p.
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Abstract

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 in situ during nuclear penetration. Native nucleosomes resolved at 5.6 [A] 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 in situ framework linking chromatin structure and dynamics to HIV-1 nuclear trafficking and provide a structural basis for viral navigation within the dynamic nuclear landscape.

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Hou, Z., Shen, Y., Shen, J., Stuart, D. I., zhang, p.. 2025-12-12. In situ chromatin dynamics and HIV-1 nuclear trafficking. https://doi.org/10.64898/2025.12.12.693995

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